Thesis final v1 2015 - for print 2016

RESISTANCE EXERCISE WITH
BLOOD FLOW RESTRICTION
An examination of the acute and chronic neuromuscular,
haemodynamic, and perceptual responses
By
Christopher Roy Brandner
Bachelor of Exercise and Sports Science (Honours)
Centre for Physical Activity and Nutrition Research
School of Exercise and Nutrition Sciences
DEAKIN UNIVERSITY
Submitted in fulfillment of the requirements of the degree of Doctor of Philosophy
December 2015

ii
DEAKIN UNIVERSITY
Access to Thesis
I am the author of the thesis entitled ‘Resistance exercise with blood flow restriction:
An examination of the acute and chronic neuromuscular, haemodynamic, and
perceptual responses’ submitted for the degree of Doctor of Philosophy.
This thesis may be made available for consultation, loan and limited copying in
accordance with the Copyright Act 1968.
'I certify that I am the student named below and that the information provided in the
form is correct'
Full Name: CHRISTOPHER ROY BRANDNER
Signed:
Date: 9th
December 2015

iii
DEAKIN UNIVERSITY
Candidate Declaration
I certify the following about the thesis entitled ‘Resistance exercise with blood flow
restriction: An examination of the acute and chronic neuromuscular, haemodynamic,
and perceptual responses’ submitted for the degree of Doctor of Philosophy that:
i. I am the creator of all or part of the whole work(s) (including content and
layout) and that where reference is made to the work of others, due
acknowledgment is given.
ii. The work(s) are not in any way a violation or infringement of any copyright,
trademark, patent, or other rights whatsoever of any person.
iii. That if the work(s) have been commissioned, sponsored or supported by any
organisation, I have fulfilled all of the obligations required by such contract or
agreement.
iv. That any material in the thesis which has been accepted for a degree or diploma
by any university or institution is identified in the text.
v. All research integrity requirements have been complied with.
I also certify that any material in the thesis which has been accepted for a degree or
diploma by any university or institution is identified in the text.
'I certify that I am the student named below and that the information provided in the
form is correct'
Full Name: CHRISTOPHER ROY BRANDNER
Signed:
Date: 9th
December 2015

iv
Abstract
The effect of blood flow restriction (BFR) in combination with light-load resistance
exercise on neuromuscular, haemodynamic, and perceptual responses, as well as
adaptations in muscle strength and mass was investigated throughout this thesis. The
primary aim was to investigate the neuromuscular, haemodynamic, and perceptual
responses following an acute bout of BFR resistance exercise (BFR-RE), as well as the
time-course adaptations following BFR resistance training (BFR-RT) and de-training,
and to determine if any observed variables were different to traditional modes of
resistance exercise/training.
Chapter four (study one) investigated the effect of an acute bout of two different types
of BFR-RE of the biceps brachii on corticomotor excitability and inhibition. Using
transcranial magnetic stimulation (TMS), it was observed that corticomotor excitability
was significantly increased 5 minutes post-exercise and remained elevated at 60
minutes post-exercise following low-pressure continuous BFR-RE. In addition,
corticomotor excitability was increased for up to 20 and 40 minutes post-exercise for
light-load resistance exercise without BFR and high-pressure intermittent BFR-RE,
respectively, but no changes were seen following heavy-load resistance exercise.
Using the same resistance exercise protocol as chapter four, chapter five (study two)
investigated the effect of BFR-RE on haemodynamic and perceptual variables. Peak-
exercising heart rate, blood pressure, cardiac output, and rate-pressure product were
significantly greater for heavy-load resistance exercise and high-pressure intermittent
BFR-RE compared with light-load resistance exercise without BFR. The magnitude of
haemodynamic responses for low-pressure continuous BFR-RE was between heavy-
load and light-load resistance exercise. In addition, ratings of perceived exertion was
higher for all trials in comparison with light-load resistance exercise, but delayed onset

v
muscle soreness was only significantly increased following the two BFR-RE trials for
up to 48 hours post-exercise.
The final project (study three) investigated the acute responses and chronic training
adaptations in corticomotor, haemodynamic, and perceptual responses, as well as
examining the adaptations in muscle strength and mass following an eight week full
body resistance training programme and four week de-training period. For ease of
interpretation, study three was divided in to two chapters. Results from chapter six
showed that lower-body and upper-body muscle strength and mass was significantly
increased over the duration of the eight week training programme regardless of blood
flow restriction, load, or volume. However, the overall magnitude of change appeared
to be greater for traditional heavy-load resistance training in comparison with BFR-RT
and light-load resistance training. In agreement with the results from chapter four, acute
increases in corticomotor excitability were observed post-exercise for BFR-RE of the
knee extensors, which were similar to heavy-load resistance training, and greater than a
non-exercise control. However, no chronic adaptation was observed for any
neuromuscular variable following training and de-training for all groups. Results from
chapter seven revealed that while the acute increase in haemodynamic responses for
BFR-RE of the knee extensors was attenuated in comparison with heavy-load resistance
exercise, no chronic adaptations were seen in these parameters at rest following
training, and only peak-exercising systolic blood pressure was decreased. Furthermore,
while ratings of perceived exertion and pain were elevated acutely following BFR-RE
at baseline, these responses were attenuated across the duration of a training
programme, suggesting a protective repeated bout effect.
Overall, results from this thesis provide some support for the efficacy of BFR-RT
regarding adaptations in muscle strength and mass. In addition, the acute and chronic

vi
adaptations in corticomotor excitability provide some evidence of central nervous
system adaptations occurring within the primary motor cortex. Furthermore, while
haemodynamic stress is attenuated during BFR-RE in comparison with heavy-load
resistance exercise, training had little effect on producing beneficial adaptations in
resting and peak-exercising responses. It was concluded that the combination of BFR
with light-load resistance exercise/training appears to be a beneficial training mode in
order to target gains in strength and muscle mass in healthy young populations, and
perhaps may be more important for special populations such as the elderly and a variety
of clinical conditions where gains in muscle strength and mass are important to obtain.

vii
Acknowledgements
First of all I would like to extend a huge thank you to my principle supervisor, Dr Stuart
Warmington. I will always be grateful that you provided me an opportunity to work
with you as part of my Honours research, and what an epic journey it has been since
then. Thank you for your guidance, sharing your knowledge, your open door policy and
always having time to discuss various issues related to research and life, most
importantly thank you also for knowing when to let your hair down and have some fun
– who else can say their supervisor started a Conga line at an International Conference!
Thank you to my associate supervisor, Dr Dawson Kidgell, this project would not have
been possible without you. I am sure that I contacted you on more than one occasion to
ask the same question because I could not get my head around it. Thank you for your
patience, guidance, ability to break things down, and also for your encouragement to
engage in and maintain a good work/life balance – a skill that I will always remember
and be sure to pass on to others. I would also like to thank Dr Timo Rantalainen for
coming on as an associate supervisor on the project, and providing valuable feedback
and support on the thesis.
I would like to thank Dr Brad Aisbett, Dr Sam Robertson, Dr Wei-Peng Teo, Brendan
Henderson, David Li, and a host of other academics within C-PAN and CESS at Deakin
University; you have all provided support at various stages throughout the project. To
my entire fellow PhD candidates both past and present, it has been an amazing journey
and I am glad to have shared it with you. Thank you to all PhD candidates that I have
shared an office space with, especially to those of you that I have worked closely with
in the Building B office. I am glad that I got to spend time with each of you, particularly
outside of the office out on the town to create some lasting memories.

viii
The final study in this project involved the recruitment of 40 participants, which
resulted in 640 supervised resistance training sessions, 320 neuromuscular and
cardiovascular testing sessions, and 320 muscle strength and mass testing sessions over
a 12 month period. Without the assistance of both Rowshan Yazdani and Ben Porteous
this research study would not have been completed to the high standard of which it was.
Thank you both so much for your hard work, and good luck to both of you in your
future endeavours. Of course, the work in this thesis would not have been possible
without the brave participants in the experiments and in the numerous pilot studies. I
owe you all a lot for your time and excellent efforts!
To my friends over the past ~6 years, thank you for always being there and allowing me
to have a fun and fulfilling life outside of sport science and research. In particular, thank
you to my best mate Craig who not only motivated me to get out of bed every day in the
early morning for gym training, but for always being there and supporting me for the
past few years through all of the highs and lows. I would also like to say a big thank
you to my new friends at Aspire Academy that have made my move overseas much
more enjoyable, and were involved in helping me to complete my thesis submission.
Finally, thank you to my family for providing all of your love and support throughout
my life. Most importantly, I am especially grateful to my parents, Roy and Jackie. This
thesis is for you, because you have always encouraged me, provided support physically,
emotionally, and financially. Everything that I have achieved I owe thanks to you, thank
you for being wonderful parents.

ix
Publications and awards
Publications arising from this thesis
A preliminary literature review and chapters four and five from this thesis have been
published. The details are as follows:
Accepted for publication:
Brandner CR. Vascular occlusion resistance training: an alternative to high resistance
strength training. Journal Australian Strength and Conditioning. 2012; 20(2): 87-96.
Brandner CR, Kidgell DJ, Warmington SA. Unilateral biceps curl hemodynamics:
Low-pressure continuous vs high-pressure intermittent blood flow restriction.
Scandinavian Journal of Medicine and Science in Sports. 2014; 25(6).
doi:10.1111/sms.12297.
Brandner CR, Warmington SA, Kidgell DJ. Corticomotor excitability is increased
following an acute bout of blood flow restriction resistance exercise. Frontiers in
Human Neuroscience, 2015; 9:652. doi: 10.3389/fnhum.2015.00652.

x
Conference presentations arising from this thesis
Australian Physiological Society (AuPS) Conference; Sydney, Australia. December
2012. Oral presentation: Acute cardiovascular responses to blood flow restriction
strength exercise.
Australian Physiological Society (AuPS) Conference; Sydney, Australia. December
2012. Poster presentation: Acute neural responses to blood flow restriction strength
exercise.
Australian Physiological Society (AuPS) Conference; Geelong, Australia. December
2013. Poster presentation: Delayed onset muscle soreness and perceptual responses to
blood flow restriction exercise.
11th
Motor Control and Human Skill Conference; Melbourne, Australia. November
2013. Oral presentation: Corticomotor responses following acute blood flow restriction
strength exercise.
6th
Exercise and Sports Science Australia (ESSA) Conference: Research to Practice;
Adelaide, Australia. April 2014. Oral presentation: Time-course of strength and muscle
thickness adaptations following 8 weeks of blood flow restriction strength training.
Finalist for the Aspire Academy Young Investigator Award for Exercise and Health.
19th
European College of Sports Science (ECSS) Conference; Amsterdam, Netherlands,
July 2014. Oral presentation: Time-course effect of blood flow restriction strength
training and detraining on haemodynamics, strength, and muscle thickness.

xi
Scientific works involving the author, but outside this thesis;
Publications
Kidgell D, Leung M, Brandner C, Spittle M, Weier A, Rantalainen T. Short-interval
intracortical inhibition is not affected by varying the complexity of an isometric task in
biceps brachii muscle. Journal of Science and Medicine in Sport 15, (2012):
Supplement 1(0): S118-S119.
Rantalainen T, Weier A, Leung M, Brandner C, Spittle M, Kidgell D. Short interval
intracortical inhibition is not affected by varying visual feedback in an isometric task in
biceps brachii muscle. Frontiers in Human Neuroscience 7, (2013),
doi:10.3389/fnhum.2013.00068.
Brandner C, Snow R, Warmington S. The effect of post exercise cold water immersion
on acclimation to exercise in the heat. Journal of Strength and Conditioning Research
12:11 (2014): 1-130, doi: 10.1519/JSC.0000000000000612.
Staunton C, May A, Brandner C, and Warmington S. Haemodynamics of aerobic and
resistance exercise with blood flow restriction exercise in young and older adults.
European Journal of Applied Physiology 115:11 (2015): 2293-2302.
Warmington S, Staunton C, May A, Brandner C. Blood flow restriction exercise: acute
versus chronic safety. European Journal of Applied Physiology. (2015) 1-2: doi:
10.1007/s00421-015-3319-1.

xii
Conference presentations
May A, Staunton C, Brandner C, and Warmington S. Australian Physiological Society
(AuPS) Conference; Geelong, Australia. December 2013. Poster presentation: The
acute haemodynamic responses of young and older men to resistance and aerobic
modes of blood-flow restriction exercise.
Brandner C, Snow R, Warmington S. 4th
National Strength and Conditioning
Association (NSCA) International Conference; Murcia, Spain. June 2014. Oral
presentation: The effect of post exercise cold water immersion on acclimation to
exercise in the heat.
Brandner C, Rantalainen T, Page B, and Warmington S. 20th
European College of
Sports Science (ECSS) Conference; Malmo, Sweden, June 2015. Oral presentation:
Neuromuscular fatigue during low-intensity isometric exercise with blood flow
restriction.

xiii
Table of contents
Access to Thesis ...............................................................................................................................ii
Candidate Declaration..................................................................................................................iii
Abstract..............................................................................................................................................iv
Acknowledgements ......................................................................................................................vii
Publications and awards .............................................................................................................ix
List of tables ..................................................................................................................................xvii
List of figures ..............................................................................................................................xviii
List of abbreviations .................................................................................................................... xx
CHAPTER ONE: Introduction............................................................................................1
1.1 Thesis aims and hypotheses................................................................................6
CHAPTER TWO: Review of the literature......................................................................8
2.1 Introduction............................................................................................................................... 8
2.2 Overview of blood flow restriction exercise................................................................12
2.2.1 Methods of application ..................................................................................13
2.2.1.1 Blood flow restriction application...............................................................14
2.2.1.2 Restriction pressure.....................................................................................17
2.2.1.3 Duration of pressure....................................................................................21
2.2.2 Exercise prescription......................................................................................23
2.2.2.1 Exercise load...............................................................................................24
2.2.2.2 Exercise volume and rest periods................................................................25
2.2.2.3 Programme frequency and duration............................................................27
2.2.2.4 Mode of exercise.........................................................................................29
2.2.2.5 Safety considerations ..................................................................................30
2.2.3 Summary........................................................................................................35
2.3 Training adaptations ............................................................................................................37
2.3.1 Muscle strength and mass ..............................................................................38
2.3.1.1 Short-term training (2-6 weeks)..................................................................40
2.3.1.2 Longer-term training (> 6 weeks)...............................................................42
2.3.1.1 De-training ..................................................................................................44
2.3.2 Mechanisms underlying hypertrophy ............................................................46
2.3.3 Muscular endurance.......................................................................................53
2.4 Neuromuscular function .....................................................................................................57
2.4.1 Techniques to measure corticomotor function...............................................59
2.4.1.1 Motor evoked potentials .............................................................................60
2.4.1.2 Paired-pulse transcranial magnetic stimulation ..........................................62
2.4.2 Acute neural responses to heavy-load resistance exercise.............................63
2.4.3 Acute neural responses to blood flow restriction resistance exercise............66
2.4.4 Chronic neural adaptations following heavy-load resistance training...........70
2.4.5 Chronic neural adaptations following blood flow restriction training...........73
2.5 Haemodynamic function .....................................................................................................76
2.5.1 Acute responses at rest...................................................................................78
2.5.2 Acute responses during exercise....................................................................79
2.5.3 Post-exercise responses..................................................................................86
2.5.4 Chronic adaptations at rest.............................................................................87
2.5.5 Chronic adaptations during exercise..............................................................90
2.5.6 Summary of findings regarding haemodynamic function..............................92
2.6 Conclusion ................................................................................................................................94
CHAPTER THREE: Materials and methods ................................................................96
3.1 Participant recruitment and ethics.................................................................................97
3.2 Anthropometric measurements.......................................................................................98
3.3 Blood flow restriction protocol.........................................................................................98

xiv
3.4 Muscle strength and mass measurements.................................................................101
3.4.1 Maximum strength.......................................................................................101
3.4.2 Muscle mass.................................................................................................101
3.4.2.1 Dual energy X-ray absorptiometry ...........................................................101
3.4.2.2 Ultrasound.................................................................................................102
3.5 Neuromuscular measurements .....................................................................................107
3.5.1 Surface electromyography ...........................................................................107
3.5.2 Transcranial magnetic stimulation...............................................................108
3.5.3 Active motor threshold ................................................................................108
3.5.4 Motor evoked potentials and short-interval intracortical inhibition ............109
3.5.5 Maximal compound muscle action potential ...............................................109
3.6 Haemodynamic measurements .....................................................................................110
3.6.1 Cardiac parameters.......................................................................................110
3.6.2 Blood pressure parameters...........................................................................111
3.7 Perceptual measurements...............................................................................................113
3.7.1 Rating of perceived exertion and pain .........................................................113
3.7.2 Delayed onset muscle soreness....................................................................114
CHAPTER FOUR: Neuromuscular responses to an acute bout of blood flow
restriction resistance exercise.....................................................................................115
4.1 Introduction..........................................................................................................................116
4.2 Methods..................................................................................................................................120
4.2.1 Participants...................................................................................................120
4.2.2 Experimental design.....................................................................................120
4.2.3 Maximal dynamic strength testing...............................................................123
4.2.4 Resistance exercise trials .............................................................................123
4.2.6 Blood flow restriction protocol....................................................................124
4.2.7 Electromyography and transcranial magnetic stimulation...........................125
4.2.7.1 Active motor threshold .............................................................................125
4.2.7.2 Motor evoked potentials and short-interval intracortical inhibition .........126
4.2.7.3 Maximal compound muscle action potential ............................................127
4.2.8 Data analyses ...............................................................................................128
4.2.9 Statistical analysis........................................................................................128
4.3 Results.....................................................................................................................................130
4.3.1 Baseline characteristics and strength ...........................................................130
4.3.2 Pre-stimulus rmsEMG and MMAX ................................................................131
4.3.3 Active motor threshold and corticomotor excitability.................................132
4.3.4 Short interval intracortical inhibition...........................................................134
4.4 Discussion..............................................................................................................................135
4.5 Conclusion .............................................................................................................................141
CHAPTER FIVE: Haemodynamic responses to an acute bout of blood flow
restriction resistance exercise.....................................................................................142
5.1 Introduction..........................................................................................................................142
5.2 Methods..................................................................................................................................147
5.2.1 Participants...................................................................................................147
5.2.3 Maximal dynamic strength...........................................................................148
5.2.4 Resistance exercise trials .............................................................................148
5.2.6 Haemodynamic measurement......................................................................150
5.2.7 Perceptual responses ....................................................................................150
5.3 Results.....................................................................................................................................152

xv
5.3.1 Haemodynamics...........................................................................................152
5.3.1.1 Cardiac parameters....................................................................................153
5.3.1.2 Blood pressures.........................................................................................156
5.3.1.3 Total peripheral resistance and rate pressure product...............................159
5.4 Discussion..............................................................................................................................163
5.5 Conclusion .............................................................................................................................168
CHAPTER SIX: Corticomotor adaptations to blood flow restriction training
and de-training ..................................................................................................................169
6.1 Introduction..........................................................................................................................170
6.2 Methods..................................................................................................................................172
6.2.1 Participants...................................................................................................172
6.2.2 Anthropometrics ..........................................................................................173
6.2.4 Resistance training programme....................................................................178
6.2.4.1 Heavy-load resistance training..................................................................179
6.2.4.2 Light-load resistance training ...................................................................179
6.2.4.3 Blood flow restriction resistance training.................................................179
6.2.5 Neuromuscular measurements.....................................................................182
6.2.5.1 Electromyography and transcranial magnetic stimulation........................183
6.2.5.2 Active motor threshold .............................................................................185
6.2.5.3 Motor evoked potentials and short-interval intracortical inhibition .........185
6.2.5.4 Stimulus response curves..........................................................................185
6.2.5.5 Maximal muscle compound action potential ............................................186
6.2.6 Measurement of muscle strength and mass..................................................186
6.2.6.1 Maximal strength testing...........................................................................186
6.2.6.2 Dual energy X-ray absorptiometry ...........................................................190
6.2.6.3 Ultrasound.................................................................................................190
6.2.7 Data analyses ...............................................................................................190
6.3 Results.....................................................................................................................................192
6.3.1 Participant characteristics ............................................................................192
6.3.2 Maximal strength .........................................................................................192
6.3.2.1 Lower-body strength.................................................................................192
6.3.2.2 Upper-body strength .................................................................................194
6.3.3 Muscle mass.................................................................................................196
6.3.2.1 Duel energy X-ray absorptiometry ...........................................................196
6.3.2.2 Muscle thickness.......................................................................................198
...............................................................................................................................199
6.3.4 Corticomotor responses and training adaptations ........................................200
6.3.4.1 Isometric strength characteristics..............................................................200
6.3.4.2 Maximal compound muscle action potential ............................................202
6.3.4.3 Corticomotor excitability..........................................................................204
6.3.4.4 Stimulus response curve............................................................................206
6.3.4.5 Short-interval intracortical inhibition........................................................208
6.4 Discussion..............................................................................................................................210
6.4.1 Acute responses in corticomotor plasticity..................................................210
6.4.2 Chronic adaptations in corticomotor plasticity............................................213
6.4.3 Adaptations in muscle strength and mass ....................................................216
6.4.4 Effects of de-training on neuromuscular function .......................................220
6.5 Conclusion .............................................................................................................................223

xvi
CHAPTER SEVEN: Haemodynamic and perceptual adaptations following
blood flow restriction training and de-training....................................................224
7.1 Introduction..........................................................................................................................225
7.2 Methods..................................................................................................................................228
7.2.1 Participants...................................................................................................228
7.2.3 Anthropometrics ..........................................................................................229
7.2.4 Resistance training programme....................................................................229
7.2.6 Measurement of haemodynamic variables...................................................229
7.3 Results.....................................................................................................................................232
7.3.1 Haemodynamic adaptations.........................................................................232
7.3.1.1 Cardiac output...........................................................................................232
7.3.1.2 Heart rate...................................................................................................234
7.3.1.3 Stroke volume ...........................................................................................236
7.3.1.4 Blood pressures.........................................................................................238
7.3.1.5 Total peripheral resistance ........................................................................244
7.3.1.6 Rate pressure product................................................................................244
7.4 Discussion..............................................................................................................................248
7.4.1 Acute haemodynamic responses during resistance exercise........................248
7.4.2 Chronic haemodynamic adaptations at rest and during exercise .................250
7.4.1 Perceptual responses following resistance training .....................................254
7.5 Conclusion .............................................................................................................................257
CHAPTER EIGHT: General discussion ......................................................................258
8.1 Evidence of early corticomotor plasticity.......................................................260
8.2 Reduced haemodynamic response in the absence of chronic adaptations......264
8.3 Acute perceptual responses not such a limiting factor for training.................267
8.4 Effects of resistance training on muscle strength and mass............................270
8.4.1 Method of blood flow restriction application ..............................................271
8.4.2 Resistance training protocol.........................................................................273
8.5 Limitations and future direction......................................................................276
8.6 Conclusion ......................................................................................................278
REFERENCES .......................................................................................................................280
APPENDICIES ......................................................................................................................309

xvii
List of tables
CHAPTER TWO:
Table 2.1 Examples of representative peak-exercising values for heart rate and blood
pressures
83
Table 2.2 Summary of acute responses and chronic cardiac and haemodynamic
adaptations to BFR-RE/RT
93
CHAPTER FOUR:
Table 4.1 Maximum strength (1-RM) and exercise workload characteristics for each
trial
124
Table 4.2 Baseline corticomotor responses and TMS variables 130
CHAPTER FIVE:
Table 5.1 Maximum strength (1-RM) and exercising workload characteristics for each
trial
152
Table 5.2 Total peripheral resistance (TPR) and rate pressure product (RPP)
responses during all four trials
160
CHAPTER SIX:
Table 6.1 Limb occlusion pressure and subsequent exercise pressures 182
Table 6.2 Anthropometric characteristics as measured at baseline 192
Table 6.3 Absolute (kg) change in body composition using Dual X-ray
Absorptiometry
197
Table 6.4 Baseline corticomotor responses and TMS variables 200
CHAPTER SEVEN:
Table 7.1 Total peripheral resistance (TPR) and rate pressure product (RPP)
responses expressed as a percentage change from rest
245

xviii
List of figures
CHAPTER TWO:
Figure 2.1 The theoretical interplay of the neural factors and hypertrophy factors
over time with resistance training
38
Figure 2.2 Schematic of the proposed interplay between potential stimuli that may
mediate the hypertrophic adaptive responses to BFR-RT
53
Figure 2.3 An overlay of five MEPs (displayed in blue) and subsequent average of
five MEPs (displayed in red) obtained from biceps brachii from a single
participant during single- and paired-pulse TMS
62
CHAPTER THREE:
Figure 3.1 The Zimmer Automatic Tourniquet System (A.T.S) 3000 99
Figure 3.2 Placement of restrictive cuffs on the lower-body (left) and upper-body
(right)
100
Figure 3.3 Example of participant and equipment set up for Dual X-ray
Absorptiometry scan (left of image), and ultrasound device (right of
image)
103
Figure 3.4 Ultrasound images representing muscle thickness for the lower-body 105
Figure 3.5 Ultrasound images representing muscle thickness for the upper-body 106
Figure 3.6 Example scale of Borgs’ ratings of perceived exertion (left) and pain
(right)
113
Figure 3.7 Example of the visual analogue scale used to measure delayed onset
muscle soreness
114
CHAPTER FOUR:
Figure 4.1 Organisation of the study 122
Figure 4.2 Visual representation of the experimental set up for TMS testing 127
Figure 4.3 MMAX amplitude following resistance exercise 131
Figure 4.4 MEP amplitude relative to MMAX following resistance exercise 133
Figure 4.5 SICI amplitude following resistance exercise 134
CHAPTER FIVE:
Figure 5.1 Organisation of the study 149
Figure 5.2 An example of participant and equipment set up for haemodynamic
testing and resistance exercise
150
Figure 5.3 Heart rate responses during all four trials 153
Figure 5.4 Cardiac output responses during all four trials 154
Figure 5.5 Stroke volume responses during all four trials 155
Figure 5.6 Systolic blood pressure responses during all four trials 156
Figure 5.7 Diastolic blood pressure responses during all four trials 157
Figure 5.8 Mean arterial blood pressure responses during all four trials 158
Figure 5.9 Perceptual responses following all four trials 162

xix
CHAPTER SIX:
Figure 6.1 Overview of the entire timeline of testing across 12 weeks for study
three
175
Figure 6.2 Overview of the acute neuromuscular, haemodynamic, and perceptual
testing measurements
177
Figure 6.3 The Zimmer Automatic Tourniquet System (A.T.S) 3000 with Limb
occlusion pressure technology
181
Figure 6.4 Visual representation of the experimental set up 183
Figure 6.5 Participant performing strength testing for the lower-body 188
Figure 6.6 Participant performing strength testing for the upper-body 189
Figure 6.7 Normalized (% change from baseline) lower- and upper-body 1-RM
responses
195
Figure 6.8 Normalized (% change from baseline) in MTH 199
Figure 6.9 Maximal voluntary isometric contraction responses measured acutely
across the duration of the 12 week study
201
Figure 6.10 Maximal compound muscle action potential responses measured acutely
across the duration of the 12 week study
203
Figure 6.11 MEP amplitude relative to MMAX following resistance exercise 205
Figure 6.12 Stimulus response curves for all groups expressed as a percentage of
MMAX
207
Figure 6.13 Short interval intracortical inhibition for all groups 209
CHAPTER SEVEN:
Figure 7.1 Participant and equipment set up for haemodynamic testing prior to knee
extension exercise
230
Figure 7.2 Cardiac output for all groups across the duration of the training
programme
233
Figure 7.3 Heart rate responses for all groups across the duration of the training
programme
235
Figure 7.4 Stroke volume responses for all groups across the duration of the
training programme
237
Figure 7.5 Systolic blood pressure responses for all groups across the duration of
the training programme
239
Figure 7.6 Diastolic blood pressure responses for all groups across the duration of
241
Figure 7.7 Mean arterial blood pressure responses for all groups across the duration
of the training programme
243
Figure 7.8 Rating of perceived exertion responses for all groups across the duration
of the training programme
246
Figure 7.9 Rating of perceived pain responses for all groups across the duration of
247

xx
List of abbreviations
1-RM One repetition maximum MAP Mean arterial pressure
ACSM American College of
Sports Medicine
MEP Motor evoked potential
AMT Active motor threshold MMAX Maximal compound
muscle action potential
ANOVA Analysis of variance MT Motor threshold
BFR Blood flow restriction MTH Muscle thickness
BFR-RE Resistance exercise with
blood flow restriction
MVIC Maximal voluntary
contraction
BFR-RT Resistance training with
blood flow restriction
PP Paired-pulse
BMI Body mass index Q̇ Cardiac output
BP Blood pressure RMT Resting motor threshold
CNS Central nervous system RPE Rating of perceived
exertion
CSA Cross sectional area RPP Rate pressure product
DOMS Delayed onset muscle
soreness
rmsEMG Root mean square
electromyography
EMG Electromyography SEM Standard error the mean
ES Effect size SICI Short-interval intracortical
inhibition
HR Heart rate SO Stimulator output
HLRE Heavy-load resistance
exercise
SP Single-pulse
HLRT Heavy-load resistance
training
SV Stroke volume
H-reflex Hoffman reflex TES Transcranial electrical
stimulation
ICF Intracortical facilitation TMS Transcranial magnetic
stimulation
ISI Inter-stimulus interval TPR Total peripheral resistance
LLRE Light-load resistance
exercise
VAS Visual analogue scale
LLRT Light-load resistance
training
V-wave Volitional wave
LOP Limb occlusion pressure
LTP Long term potentiation
M1 Primary motor cortex

2
Traditionally it was expected that in order to induce maximal gains in muscle strength
and mass following a resistance training programme, heavy-loads equivalent to ≥ 65%
of an individual’s one repetition maximum (1-RM) are required to be lifted (Kraemer et
al., 2002, Kraemer and Ratamess, 2004, Folland and Williams, 2007, Tan, 1999,
Medicine, 2013). However, more recent evidence has shown that when light-loads (20-
30% 1-RM) are lifted in combination with blood flow restriction (BFR) induced via
inflatable pressure cuffs, the gain in muscle strength and mass are greater compared
with light-load resistance training (LLRT) without BFR (Abe et al., 2012, Takarada et
al., 2000c, Yasuda et al., 2010b). In addition, the gains observed following BFR
resistance training have been shown to be similar to traditional heavy-load resistance
training (HLRT) (Clark et al., 2010, Karabulut et al., 2011a, Laurentino et al., 2012,
Takarada et al., 2000c, Thiebaud et al., 2013a). This relatively unique mode of
resistance training has been shown to produce significant gains in muscle strength and
mass in young healthy untrained populations (Abe et al., 2005c, Yasuda et al., 2010b),
trained athletes (Cook et al., 2013, Abe et al., 2005b), and perhaps of more importance,
has been shown to be beneficial for clinical populations with limited resistance training
capacities such as the elderly (Ozaki et al., 2011a, Abe et al., 2010, Fry et al., 2010,
Takarada et al., 2000c, Sakamaki et al., 2008), patients in early rehabilitation following
injury (Loenneke et al., 2012g, Ohta et al., 2003, Takarada et al., 2000b), or where
muscle atrophy and weakness occur due to the effects of inactivity or disease (Cook et
al., 2010, Cook et al., 2014). As such, a greater understanding of the physiological
responses and adaptations following BFR resistance exercise (BFR-RE) and resistance
training (BFR-RT) should be of interest. In this thesis, the history of BFR-RT including
important past events and methodological issues related to BFR application and
exercise prescription are presented. More specifically, the purpose of this thesis was to

3
examine the acute (exercise) and chronic (training) adaptations in the neuromuscular,
cardiovascular, and perceptual responses to BFR-RE and BFR-RT.
The vast majority of the current literature has focussed on the efficacy of BFR-RT in
regards to muscular function (i.e. adaptations in muscular strength, mass, and
endurance), yet relatively little is known regarding the neuromuscular adaptations that
underpin the increase in maximal strength (Karabulut et al., 2007). Despite the use of
light-loads prescribed during BFR-RE, previous studies have observed acute increases
in surface electromyography (EMG) similar to heavy-load resistance exercise (HLRE)
(Takarada et al., 2000c, Yasuda et al., 2008), and significantly higher muscle activity in
comparison with load matched controls (Moritani et al., 1992, Yasuda et al., 2006). This
effect has been speculated to be due to activation of group III and IV muscle afferent
fibres (Yasuda et al., 2010a), which may provide feedback to the primary motor cortex
(M1) in order to modulate force output during the resistance exercise bout. While there
are currently no studies that have used the correct technique to measure M1 output
during or following an acute bout of BFR-RE, several studies (Ridding and Rothwell,
1995, Brasil-Neto et al., 1993b, Brasil-Neto et al., 1993a, Vallence et al., 2012,
Ziemann et al., 1998a, Ziemann et al., 1998b) have shown that ischemic nerve
deafferentation (without exercise) acutely modifies corticomotor excitability and short-
interval intracortical inhibition (SICI) as measured with transcranial magnetic
stimulation (TMS). Furthermore, there have been reports of increased corticomotor
excitability and decreased SICI following acute HLRE (Carroll et al., 2008, Sacco et al.,
1997, Selvanayagam et al., 2011, Leung et al., 2015) and short-term HLRT programmes
(Goodwill et al., 2012, Kidgell et al., 2010, Weier et al., 2012), suggesting that
adaptations in muscle strength following training may be driven by plastic changes
within the M1. Despite evidence of the increase in muscular strength being similar

4
between HLRT and BFR-RT, there have been no attempts to measure adaptations in
M1 plasticity following short- and long-term resistance training programmes using
TMS.
Another aspect of BFR-RE/RT that has received considerable attention is the effect on
haemodynamic responses (Pope et al., 2013, Loenneke et al., 2011b, Horiuchi and
Okita, 2012). So far, it appears that BFR-RE significantly increases in heart rate, blood
pressure, cardiac output, as well as a decrease in stroke volume. Most of the current
literature has shown that these responses are higher in comparison than light-load
resistance exercise (LLRE) without BFR (Hollander et al., 2010, Patterson and
Ferguson, 2010, Takano et al., 2005, Vieira et al., 2012), but a more thorough
examination of the upper- and lower-body responses in comparison with HLRE is
required. Furthermore, despite the known increases in muscle strength, mass, and
endurance following BFR-RT, much less is known about the haemodynamic
adaptations that occur following short- and long-term BFR-RT programmes (Fahs et al.,
2011a, Kacin and Strazar, 2011, Kim et al., 2009, Ozaki et al., 2012). Due to the nature
of the BFR whereby blood flow is altered, several studies have focussed on the acute
and chronic responses in vascular function rather than the haemodynamic responses. In
addition, because BFR can be used in combination with aerobic exercise such as
walking and cycling (Park et al., 2010, Ozaki et al., 2011a) this has also received
greater attention in comparison with the haemodynamic responses following resistance
exercise/training. Ultimately, for BFR-RE/RT to be recommended as a safe and
efficacious alternative to HLRT for young healthy populations, as well as clinical
populations, then an examination of the acute and chronic haemodynamic responses to
upper- and lower-body BFR-RE/RT are required.

5
One of the main criticisms to this type of resistance exercise/training is that despite the
use of light-loads, BFR-RE causes relatively high increases in perceptual responses
such as ratings of perceived exertion (RPE) and pain during exercise, as well as
inducing delayed onset muscle soreness (DOMS) for up to 48-72 hours post-exercise
(Hollander et al., 2010, Loenneke et al., 2010a, Wernbom et al., 2006, Wernbom et al.,
2009, Vieira et al., 2014, Fitschen et al., 2013, Rossow et al., 2012, Umbel et al., 2009).
Furthermore, in comparison with traditional HLRE, perceptual responses during BFR-
RE have produced contrasting results whereby they have been shown to be similar
(Hollander et al., 2010), higher (Vieira et al., 2014, Loenneke et al., 2015), and lower
(Yasuda et al., 2010a) for BFR-RE depending on the exercise prescription utilized (i.e.
loads, total repetitions, and BFR variables such as cuff pressure and duration). While
the acute perceptual responses for BFR-RE are typically higher in comparison with
LLRE (Hollander et al., 2010, Loenneke et al., 2010a, Wernbom et al., 2006, Wernbom
et al., 2009, Fitschen et al., 2013), when the exercise bout is repeated over a training
period these perceptual responses subside, suggesting a repeated bout effect (Fitschen et
al., 2013).
Current evidence suggests that BFR-RT produces similar gains in muscle strength and
mass in comparison with HLRT (Clark et al., 2010, Karabulut et al., 2011a, Laurentino
et al., 2012, Takarada et al., 2000c, Thiebaud et al., 2013a). Yet to the authors’
knowledge, the underlying neuromuscular adaptations responsible for these adaptations
in muscle strength are relatively unknown. Considering evidence from acute BFR-RE
studies, ischemic nerve deafferentation literature, and recent short-term HLRT studies,
it is possible that BFR-RE/RT results in modifications within the M1 that are
responsible for the adaptations in muscle strength following a training programme. In
addition, while this type of training may be recommended as a potential alternative to

6
HLRT for those who are unable to lift heavy-loads, the elevated increases in
haemodynamic and perceptual responses may be of some concern. Therefore, the
purpose of this thesis was to examine the efficacy of BFR-RE on acute neuromuscular,
haemodynamic, and perceptual responses (two studies). In addition, the long-term
adaptations in these variables following BFR-RT were also of interest (one study), with
the overarching goal of enhancing muscular strength and mass.
1.1 Thesis aims and hypotheses
The primary aim of this thesis was to determine the efficacy of BFR resistance exercise
and training on neuromuscular, haemodynamic, and perceptual responses, as well as
gaining a greater understanding of the adaptations in muscle strength and mass
following BFR resistance training.
The specific aims of this thesis, which were addressed by each study chapter, were:
i. To examine the acute responses in corticomotor excitability and inhibition using
TMS following a single bout of BFR-RE of the elbow flexors (chapter four,
pages 115-141).
ii. To examine the acute haemodynamic and perceptual responses following a
single bout of BFR-RE of the elbow flexors (chapter five, pages 142-168).
iii. To investigate adaptations in muscle strength and mass following an eight week
full-body BFR-RT and four week de-training program (chapter six, pages 169-
223).
iv. To investigate the acute responses and also time-course adaptations in
corticomotor excitability and inhibition following an eight week full-body BFR-
RT and four week de-training program (chapter six, pages 169-223).

7
v. To investigate the acute responses and also time-course adaptations in
haemodynamic function and perceptual responses following an eight week full-
body BFR-RT and four week de-training program (chapter seven, pages 223-
257).
It was hypothesised that:
i. An acute bout of BFR-RE of the elbow flexors would produce a greater increase
in corticomotor excitability and reduction in inhibition compared to LLRE,
similar to the responses observed following an acute bout of HLRE (chapter
four, pages 115-141).
ii. An acute bout of BFR-RE of the elbow flexors would result in lower
haemodynamic and perceptual responses in comparison with an acute bout of
HLRE (chapter five, pages 142-168), with the responses being similar to LLRE.
iii. The application of BFR during a resistance training programme would produce
progressive increases in muscle strength and mass similar to HLRT following
eight weeks of training, with these changes being maintained during four weeks
of de-training. In addition, the change in muscle strength would be accompanied
by increases in corticomotor excitability and a reduction in inhibition (chapter
six, pages 169-223).
iv. An acute bout of BFR-RE of the knee extensors would result in lower
haemodynamic responses in comparison with HLRE, with the responses being
similar to LLRE. In addition, perceptual responses in exertion and pain would
be similar between BFR-RE and HLRE, with both being higher than LLRE.
Secondly, the peak exercising haemodynamic responses would attenuate
following an eight week full-body BFR-RT programme similar to HLRT
(chapter seven, pages 224-257).

8
CHAPTER TWO:
Review of the literature

9
2.1 Introduction
It is well established that resistance training increases maximal strength and induces
hypertrophy of skeletal muscle (Kraemer et al., 2002). It has been recommended that in
order to maximise the gain in muscle strength and mass, a training program should
include multiple sets of 6-12 repetitions utilizing heavy-loads corresponding to ≥ 65%
of an individual’s one repetition maximum (1-RM) (Kraemer et al., 2002, Kraemer and
Ratamess, 2004, Folland and Williams, 2007, Tan, 1999, ACSM, 2013). In comparison,
when a higher number of repetitions (i.e. ≥ 15; but not maximal repetitions to failure)
are performed utilizing light-loads (≤ 50% 1-RM), the primary adaptation to training is
an increase in local muscular endurance without any significant increase in muscle
strength or mass (Campos et al., 2002, Stone and Coulter, 1994). However, recent
evidence suggests that when light-load resistance training (LLRT) is combined with
blood flow restriction (BFR), that strength and muscle mass may increase to a similar
extent as traditional heavy-load resistance training (HLRT) (Clark et al., 2010,
Karabulut et al., 2011a, Laurentino et al., 2012, Takarada et al., 2000c, Thiebaud et al.,
2013a). At present, this mode of resistance exercise/training is relatively new (Sato,
2005), with the first English language scientific research article printed in 1998
(Shinohara et al., 1998). However, while further investigation of the efficacy and safety
of BFR exercise is required, current evidence suggests that it may be a viable alternative
to HLRT as a means of increasing muscle strength and mass. A better understanding of
BFR resistance exercise (BFR-RE) and resistance training (BFR-RT) may have
important implications for healthy populations that require rapid gains in muscle
strength and mass, or for populations that have limited resistance training capacities
such as the elderly (Abe et al., 2010, Takarada et al., 2000c), patients in early
rehabilitation following injury (Ohta et al., 2003, Takarada et al., 2000b), or where
muscle atrophy and weakness occur due to the effects of inactivity or disease (Cook et

10
al., 2010, Cook et al., 2014). Therefore, to induce strength and hypertrophy, training
modalities that promote these two adaptations to resistance training without the use of
heavy-loads should be of interest.
To date, the effects of BFR-RT on increasing muscle strength have been well
documented (for recent reviews see Pope et al., 2013 and Scott et al., 2014). However,
the underlying neuromuscular mechanisms that may underpin these changes in strength
are less well understood (Karabulut et al., 2007). Previous studies have established
peripheral outcome measures such as increased muscle activity via surface
electromyography (EMG), and concluded that BFR-RE/RT alters neural drive to muscle
(Takarada et al., 2000c, Yasuda et al., 2006, Moritani et al., 1992, Yasuda et al., 2009).
However, no study has directly measured the functional properties of the corticomotor
pathways shown to modulate voluntary force production. Therefore, our current
understanding of BFR-RE/RT is limited in that little information with regard to
corticomotor function is known.
While HLRT may be the most effective technique for developing muscle strength, mass
and functional capacity, this mode of resistance exercise induces a high acute
haemodynamic stress (in particular, a substantial increase in blood pressure response)
(Fleck, 1988, Fleck, 1992). Therefore, HLRT may only be cautiously prescribed to
clinical or elderly populations, particularly those with existing neuromuscular,
cardiovascular, and metabolic diseases. If BFR-RE/RT is to be recommended as a
suitable low risk alternative to HLRT, yet with moderately equivalent outcomes, then a
greater understanding of the impact BFR has on the cardiovascular system is warranted.
In particular, investigations of the acute haemodynamic responses to BFR-RE and how
these adapt to progressive training in comparison with traditional HLRT are necessary

11
to increase our understanding of the responses so that this mode of exercise may be
recommended for use in both healthy and clinical populations.
This introducing chapter begins with an overview of how BFR-RE/RT is traditionally
performed, and the resulting training adaptations to muscle strength, mass, and
endurance. This is followed by a detailed analysis of the current evidence and
underlying neuromuscular mechanisms responsible for the increase in strength
following traditional HLRT as well as BFR-RE/RT, and a summary of the techniques
used to assess corticomotor function. Finally, the effect of BFR-RE/RT on
haemodynamics will also be explored.

12
2.2 Overview of blood flow restriction exercise
Resistance training with blood flow restriction (BFR) was popularized in Japan by
Dr. Yoshiaki Sato in the 1980’s, where it is known as Kaatsu training (Sato, 2005).
For more information about the history of Kaatsu, the reader is directed to a paper by
Sato (2005). Briefly though, Dr. Sato first received inspiration for the technique in
1966 as a result of feeling numbness in his leg musculature after kneeling for long
periods of time, and soon after began experimentation to replicate the muscle
pump/swelling. In 1970, the basic Kaatsu training manual was completed, and
became widely available for public use in Japan in 1983 when a prototype Kaatsu
device was created. In December 2003, the commonly used Kaatsu Master device
was developed and has been extensively used in the field (Nakajima et al., 2006) and
in research (Takarada et al., 2000c, Takano et al., 2005, Abe et al., 2005c, Yasuda et
al., 2005, Ishii et al., 2005, Abe et al., 2006, Nakajima et al., 2006). However, the
intellectual property of using Kaatsu, including the specialized pneumatic equipment
and certification, recently received copyright and patent protection in Japan, Europe
and America (Weatherholt et al., 2012). As a result, it is difficult to obtain use of the
device for exercise in the field and research outside of Japan. Therefore, a range of
other devices are used during exercise and training and is more commonly referred to
as BFR.
BFR is performed by placing a restrictive cuff (usually pneumatic) around the most
proximal portion of a limb prior to exercise, where it is then inflated to a pressure
where arterial blood flow is restricted with venous blood flow fully occluded
(Loenneke et al., 2013a, Fahs et al., 2012, Pope et al., 2013). The use of a
commercially manufactured BFR device as a training intervention is relatively new
(Sato, 2005) with the first the first English language scientific research article printed

13
in 1998 (Shinohara et al., 1998), however exercise under ischemic conditions has
been investigated in the scientific literature since at least the 1960s (Fales et al., 1962,
Moritani et al., 1992, Chiu et al., 1976, Larsson and Hultman, 1979). The novelty of
BFR exercise is that relatively light-loads during a bout of resistance exercise (i.e.
20-50% 1-RM) or low-intensities (i.e. 3-5 km.hr-1
) during aerobic exercise are
utilized, yet these elicit gains in muscle strength and mass. Interestingly, the increase
in muscle strength and mass observed following BFR-RT are typically greater than
LLRT without BFR (Abe et al., 2012, Fahs et al., 2012, Loenneke et al., 2011c), and
may be similar to traditional HLRT (Clark et al., 2010, Karabulut et al., 2011a,
Laurentino et al., 2012, Takarada et al., 2000c, Thiebaud et al., 2013a). This work has
challenged the notion that heavy-loads or high-intensities are required during
resistance or aerobic exercise to increase strength and muscle mass, resulting in
overall improvements in muscle functional capacity (Kraemer et al., 2002, Folland
and Williams, 2007, Baechle and Earle, 2008). BFR-RE/RT has therefore been
recommended for use in healthy populations, as well as some clinical populations
where muscle atrophy or weakness is present due to inactivity or disease.
With the added aspect of applying restrictive cuffs during BFR-RE/RT, there are
several modifiable variables in regards to methods of application and prescription of
exercise that will affect the degree of acute responses and training adaptations to
BFR-RE/RT. Therefore, the purpose of sections 2.2.1 to 2.2.3 (pages 13-36) is to
summarise the different methodologies used in the BFR literature.
2.2.1 Methods of application
There is currently no standard method for the application of BFR during exercise. Many
differences exist in the restrictive cuff type (size and material), final restrictive pressure
used during exercise, and the duration of the restrictive pressure applied, all of which

14
may affect the quality of BFR during exercise (Fahs et al., 2012, Scott et al., 2014).
Furthermore, while generalized procedures were used in the early research (i.e. between
1998-2012) for determining cuff pressures during exercise, more recent research
suggests that the final exercising cuff pressure should be individualized to each
participant/user. Manipulation of the BFR protocol applied during resistance
exercise/training has been shown to affect the neuromuscular, endocrine,
haemodynamic, and perceptual responses; therefore, the variables that affect the degree
of BFR should be of interest. For detailed reviews on the methodological considerations
for BFR exercise, the reader is directed to reviews by Fahs et al., (2012), Loenneke et
al., (2011e), Abe et al., (2012), and Scott et al., (2014).
2.2.1.1 Blood flow restriction application
Prior to the commercial use of Kaatsu equipment, Dr. Sato initially performed Kaatsu
exercise/training using elastic bicycle tubing (Sato, 2005). In the BFR literature a
number of different devices have been used to restrict blood flow during exercise,
including elastic knee wraps (Loenneke et al., 2010a, Loenneke et al., 2010b, Loenneke
et al., 2011e), elastic belts with a pneumatic bag inside (Rossow et al., 2011, Fahs et al.,
2011b), or traditional nylon blood pressure cuffs (Laurentino et al., 2008, Teramoto and
Golding, 2006, Cook et al., 2007, Manini et al., 2012). Anecdotal evidence also
suggests that professional and recreational athletes around the world have been
improvising using homemade tourniquets for a number of years. However, this practice
is not generally recommended because of the uncertainty surrounding the pressures
being applied, and using the correct pressure is one of the fundamental aspects of BFR-
RE/RT. Many research studies have used the Kaatsu Master or Kaatsu Mini (Sato
Sports Plaza, Tokyo, Japan) during BFR-RE/RT (Takarada et al., 2000c, Takano et al.,

15
2005, Abe et al., 2005c, Yasuda et al., 2005, Ishii et al., 2005, Abe et al., 2006,
Nakajima et al., 2006). The Kaatsu Master is available for use with elastic restrictive
cuffs, which are typically 3 cm or 5 cm wide for upper- and lower-body exercise,
respectively. A limitation of this device however is that the Kaatsu training centre in
Tokyo has the patent on the device and it is difficult to obtain for use outside of Japan
(Weatherholt et al., 2012). Until recently, the American College of Sports Medicine
(ACSM) offered Kaatsu training research grants, which allowed for the use of the Sato
Sports Plaza equipment and ACSM approved Kaatsu training for grant winners. It
currently appears that these are no longer available. Therefore, it would seem that
studies investigating BFR have produced the restriction using wrapping devices like a
pneumatic restriction cuff, in combination with an external mechanical pressure device
which allows for precise pressure control.
Unfortunately, in much of the literature, the width of the restrictive cuff used for BFR is
not often reported. From the available evidence, the restrictive cuff widths that have
been utilized range from 2 cm for the upper-body to 20.5 cm for the lower-body (Fahs
et al., 2012, Loenneke et al., 2011c). This is an important factor to consider, since it has
been shown that wider cuffs provide a more effective transmission of pressure through
the soft tissue compared with narrow cuffs (Crenshaw et al., 1988, Graham et al., 1993,
Shaw and Murray, 1982). Therefore, this may impact the efficacy of neuromuscular,
endocrine, haemodynamic, and perceptual responses and adaptations to
exercise/training. In an early study by Crenshaw et al., (1998), it was observed that
wider cuffs (18 cm) likely occluded arterial blood flow at a lower overall pressure in
comparison with narrow cuffs (4.5 cm). Similar results for arterial occlusion pressures
for the lower-body have been confirmed by Graham et al., (1993) and Loenneke et al.,
(2011c), and also arterial occlusion pressures for the upper-body (Moore et al., 1987).

16
Currently, there is a lack of available evidence that compares the physiological
responses to BFR-RE/RT using different cuff widths. Rossow et al., (2012) compared
BFR knee extension exercise (20% 1-RM) using a 13.5 cm wide nylon penumatic cuff
(Hokanson E20 Rapid Cuff Inflator, Bellevue, WA, USA) and a 5 cm elastic pneumatic
cuff (Kaatsu Master, Sato Sports Plaza, Tokyo, Japan). Both cuffs were inflated during
exercise to a final pressure of 130% resting systolic blood pressure. The wider cuffs
caused a greater elevation in cardiovascular measurements (e.g. heart rate and blood
pressure) and also increased ratings of pain and perceived exertion during exercise, in
comparison with the narrow cuffs. Based on this evidence, it should be expected that
when using wider restrictive cuffs for BFR-RE/RT the final exercise pressure should be
lower compared with narrow restrictive cuffs in order to maintain exercise volume
without inducing pain while still providing the same level of restriction to blood flow.
The aim of this section is not to compare training adaptations between wide and narrow
restrictive cuffs. To the authors’ knowledge, there have been no training studies that
have examined this. However, it is important to note that regardless of cuff width, it
would appear that BFR-RT increases muscle strength, mass, and endurance. For more
information regarding the potential training adaptations following BFR-RT, the reader
is directed to section 2.3 (page 37).
With regards to the type of material the cuff is made from, it would appear that both
nylon and elastic cuffs are the preferred materials used in the BFR literature (Loenneke
et al., 2013a). From the available evidence, both nylon and elastic cuff types of the
same width produce the same level of arterial occlusion pressure as measured by
Doppler ultrasound when inflated to the same pressure (Loenneke et al., 2013b). In a
follow up study by the same authors, they reported no difference in the number of
repetitions to muscular failure or ratings of perceived exertion between the nylon and

17
elastic cuffs (Loenneke et al., 2014e). While there is a lack of research investigating the
effect of cuff material on the physiological responses/adaptations to BFR-RE/RT, the
current evidence suggests that both elastic and nylon cuffs of the same width and
pressure should cause similar degrees of BFR, and would be expected to result in
similar training adaptations. Based on these results, it is recommended that the final
exercise pressure used during BFR-RE/RT should account for the restrictive cuff width,
but not type of cuff material.
2.2.1.2 Restriction pressure
There is no consensus within the literature as to what the optimal final cuff pressure for
use during BFR-RE/RT. It was previously common practice in the BFR literature to
apply arbitrary pressures for each participant prior to using BFR. For example,
pressures of up to ~300 mmHg have been shown to completely occlude blood flow to
the quadriceps (Cook et al., 2007), while pressures lower than diastolic blood pressure
(i.e. ≤ 80 mmHg) that may allow for some circulatory inflow to exercising muscle have
also been used (Takarada et al., 2000c, Sumide et al., 2009, Burgomaster et al., 2003,
Ishii et al., 2005). This is problematic in that the same arbitrary pressures applied to
each individual will differ in the physiological and perceptual responses due to various
distinct physical and methodological differences. As an example, five studies utilized a
BFR pressure of 200 mmHg to measure physiological responses to exercise/training
(Moritani et al., 1992, Ozaki et al., 2011b, Sakamaki et al., 2008, Takarada et al., 2002,
Wernbom et al., 2006). Three of these studies (Ozaki et al., 2011b, Sakamaki et al.,
2008, Takarada et al., 2002) utilized narrow cuffs (5 cm) during lower-body BFR
exercise, one study used a wide (13.5 cm) cuff during knee extension exercise
(Wernbom et al., 2006), and the final study (Moritani et al., 1992) did not record the

18
width of the cuff used during an isometric handgrip task. This highlights that different
sized limbs (i.e. both muscle and adipose tissue), vasculature, and exercises were
performed between studies despite using the same cuff pressure. This may not only
decrease the efficacy of BFR with regard to training adaptations, but it may also be a
safety concern, particularly if the pressures used are too high (i.e. those that result in
complete vascular occlusion) (Loenneke et al., 2013a). In addition, the use of varying
cuff pressures (in combination with different cuff widths, and prescription of exercise)
during different BFR studies makes it difficult to determine the most appropriate
method. Even Dr. Sato acknowledged (Sato, 2005) that he found it difficult to apply the
appropriate pressure for himself and other individuals during early experimentations, to
a point where his skin would turn pale and was later diagnosed with pulmonary
embolism, possibly due to his experimentations, however there is no evidence of this
and may just be coincidental. Therefore, he noted that each individual required unique
attention, and attributed differences in BFR pressure to the participants age, size of the
blood vessels, size of the limbs including muscle and adipose tissue, and current
strength capacity (Sato, 2005). The following explores more recent methods used to
potentially individualize cuff pressures during BFR.
There have been several research papers attempting to individualize BFR pressures
based on participants’ resting brachial blood pressure (Downs et al., 2014, Yasuda et
al., 2006, Karabulut et al., 2010b, Clark et al., 2010). A common approach was to use
pressures generally higher than resting brachial systolic blood pressure (140-180
mmHg), or approximately 30% above resting brachial systolic blood pressure (Takarada
et al., 2002, Sumide et al., 2009, Takano et al., 2005, Laurentino et al., 2008, Yasuda et
al., 2006, Abe et al., 2005b). It was suggested that when applied under resting
conditions (i.e. no muscular contractions) a pressure 30% above resting brachial systolic

19
blood pressure fully occludes venous blood flow and so causing pooling in the
capacitance vessels distal to the cuff, while also limiting (but not fully occluding)
arterial blood flow (Takarada et al., 2000c). For example, Takano et al., (2005)
demonstrated that femoral artery blood flow in a supine position was reduced from 370
± 71 to 133 ± 38 ml/min. Another study compared the effect of different pressures
during BFR over eight weeks (Sumide et al., 2009). Participants were randomly
allocated to BFR of either 50 mmHg (below resting diastolic pressure), 150 mmHg
(above resting systolic pressure) or with a supramaximal BFR pressure of 250 mmHg.
Following training, each group showed a similar significant increase in strength.
However, of note though, subjects in the supramaximal BFR group complained of
discomfort and numbness in their legs during BFR (Sumide et al., 2009). In addition,
the application of wide cuffs (13 cm) coupled with high restriction pressures (230
mmHg) during knee extension exercise have also been shown to result in reduced
quadriceps CSA at the site of muscle origin, possibly due to the high compression and
shear stress under the cuff (Kacin and Strazar, 2011). Further evidence from a recent
meta-analysis indicate that higher restriction pressures (≥ 180 mmHg) are no more
effective than lower pressures for inducing training adaptations (Loenneke et al.,
2011f).
While the use of brachial systolic blood pressure was thought to provide a practical
approach for determining restriction pressures during exercise, evidence from several
investigations have examined a lack of relationship between brachial systolic blood
pressure and participants arterial limb occlusion pressure (LOP) (Loenneke et al.,
2011c, Crenshaw et al., 1988, Shaw and Murray, 1982, Van Roekel and Thurston, 1985,
Graham et al., 1993, Downs et al., 2014). Moore et al., (1987) first determined that LOP
was strongly related to cuff width, but not brachial systolic blood pressure or upper-

20
body limb circumference. In agreement, Crenshaw et al., (1988) found that regardless
of cuff width, brachial systolic blood pressure did not affect an individual’s LOP.
However, in contrast, Graham et al., (1993) observed a constant inverse relationship
between seven different cuff widths and LOP for both the lower- and upper-body.
Further to this, Loenneke et al., (2011d) recently sought to determine what factors
should be accounted for when prescribing BFR pressures for the lower-body during
exercise/training. Measurements of participants’ mid-thigh muscle and fat CSA, leg
circumference, ankle brachial index, and brachial blood pressure were taken prior to
measurement of LOP being obtained with both wide and narrow cuffs. As mentioned
previously, the wide cuffs fully occluded blood flow at lower pressures (144 ± 17
mmHg) compared with narrow cuffs (235 ± 42 mmHg). In addition, liner regression
analysis determined that both thigh composition (lab method) and thigh circumference
(field method), along with ankle brachial index and brachial diastolic blood pressure
were the best predictors of LOP when using wide cuffs. In contrast, for narrow cuffs the
best predictors of LOP were thigh circumference and composition, as well as brachial
diastolic blood pressure. In a follow up study by the same authors (Loenneke et al.,
2014c), in the largest study of its kind in the BFR literature (171 participants) it was
concluded that both arm circumference and systolic blood pressure should be taken into
account when determining BFR pressures for the upper-body. Given the known
differences in cuff widths to determine the LOP, it should also be noted that the cuff
width used to determine an individuals’ LOP should be the same size as the cuff used to
restrict blood flow during the exercise bout. For algorithms to calculate the appropriate
cuff pressure for use during BFR, the reader is directed to work by Loenneke et al.,
(2014c).

21
In summary, while the most beneficial final cuff pressure used during BFR-RE/RT is
still unknown, it would appear that the chosen BFR pressure should be high enough to
restrict arterial inflow, while occluding venous outflow (Loenneke et al., 2013a, Fahs et
al., 2012, Pope et al., 2013). Research has shown that high BFR pressures (particularly
with wide cuffs) are not required during BFR to induce beneficial adaptations, and can
cause increases in muscle pain and perceived exertion, while limiting the volume (sets x
repetitions) of training. Therefore, BFR pressures should be individualized for
participants, whereby it is recommended that the LOP be obtained at rest, while
subsequently using 50-80% of LOP to set the BFR pressure during exercise (Laurentino
et al., 2008, Laurentino et al., 2012, Gualano et al., 2010a, Gualano et al., 2010b, Neto
et al., 2014b).
2.2.1.3 Duration of pressure
BFR-RE/RT studies do not often specify the duration of the applied restriction. The
continuous application of BFR throughout an entire set of exercises/contractions,
including the rest periods, appears to be most common (Takarada et al., 2000c,
Takarada et al., 2002, Sumide et al., 2009, Takano et al., 2005, Cook et al., 2007,
Yasuda et al., 2005, Ishii et al., 2005). During BFR, three to five sets of each exercise
are completed for a high number of repetitions (≥ 15) or to volitional fatigue, with rest
periods between sets as short as 30 seconds, and no longer than 1 minute in length (Fahs
et al., 2012, Loenneke et al., 2011f, Scott et al., 2014). Therefore, continuous
application of BFR is only sustained for a short period (≤ 15 min) due to the nature of
the resistance exercise. However, releasing the pressure at the completion of each
exercise set has also been utilized (Cook et al., 2007, Laurentino et al., 2008, Moritani
et al., 1992, Pierce et al., 2006, Wernbom et al., 2006), and this is likely to allow for

22
some reperfusion of muscle between sets, as well as reducing muscle fatigue (Cook et
al., 2007) and perceived pain (Fitschen et al., 2013).
There is limited available evidence to suggest which method (i.e. continuous versus
intermittent BFR application) has the greatest effect on neuromuscular, endocrine,
haemodynamic, and perceptual responses, or which produces greater muscular benefits.
It has been suggested that intermittent BFR may be preferable to continuous BFR due to
lower levels of perceived pain being reported (Fitschen et al., 2013, Wernbom et al.,
2008). Indeed, Fitschen et al., (2013) showed that knee extension exercise to muscular
failure with intermittent BFR was less painful than continuous BFR. While in contrast,
continuous BFR has been shown to be more effective at increasing intramuscular
metabolic stress and fast twitch fiber recruitment compared with intermittent BFR
(Suga et al., 2012). Furthermore, the responses following continuous BFR were similar
to heavy-load resistance exercise (Suga et al., 2012). With regard to neuromuscular
responses, muscle activation patterns measured using EMG during BFR elbow flexion
exercise (20% 1-RM) have been observed to be similar between continuous and
intermittent BFR (Yasuda et al., 2013). While during a study comparing different BFR
pressures (~160 versus ~300 mmHg), durations (continuous versus intermittent) and
external loads (20% 1-RM versus 40% maximal isometric voluntary contraction
[MVIC]) it was shown that all protocols elicited as much fatigue as a heavy-load trial
(80% MVIC) (Cook et al., 2007). However, the continuous BFR with 160 mmHg
protocol resulted in significantly higher levels of muscle fatigue compared with the
heavy-load condition. This is an important factor, because the processes contributing to
muscle fatigue has been associated with beneficial adaptations to muscle strength and
mass following resistance training (Rooney et al., 1994). To date, only one study has
examined the training adaptations comparing continuous versus intermittent application

23
of BFR (Fitschen et al., 2013). Participants completed a five week resistance training
protocol consisting of leg press, leg extension, and seated hamstring curls at 30% 1-
RM, as well as bodyweight calf raises. Training was completed three times per week,
and BFR was applied using a 5 cm cuff attached to a Kaatsu Mini at a pressure of 160
mmHg. While the investigators found significant increases in knee extension (5.2%)
and flexion (6.4%) strength, these were not different between the two BFR protocols. In
addition, using Dual X-ray absorptiometry (DXA) no changes in lean muscle mass were
found for either group across the duration of the study. While the application of BFR
during rest intervals is recommended as an important training variable, results from this
study suggest that continuous BFR has little additional benefit over intermittent BFR,
but the latter protocol is less painful (Fitschen et al., 2013). Therefore, more studies are
needed to validate the importance of BFR duration during an acute resistance exercise
session on the effects of muscle strength and hypertrophy.
2.2.2 Exercise prescription
As mentioned in section 2.2.1 (pages 13-23), while the different methods of BFR
application will affect the degree of efficacy of BFR-RE/RT, it should also be of
interest to examine the different BFR exercise protocols that may affect the
physiological responses to an acute bout of BFR exercise, and following short- and
long-term training programmes. In the BFR literature there exist many differences with
regard to training variables, including; exercise intensity, exercise volume, mode of
exercise, frequency, duration, days per week, and mode of exercise (Loenneke et al.,
2011f, Fahs et al., 2012, Scott et al., 2014). These variables are reviewed in the
following sections.

24
2.2.2.1 Exercise load
Intensity or load is generally regarded as the most important variable in the prescription
of resistance training (Tan, 1999, Folland and Williams, 2007, Kraemer et al., 2002).
The intensity of dynamic resistance training is often quantified as a function of the
maximum weight that can be lifted only once (i.e. 1-RM or MVIC) (Kraemer et al.,
2002). Typically, to gain strength and induce hypertrophy of skeletal muscle it has been
recommended that loads ≥ 65% 1-RM should be utilized (Kraemer et al., 2002,
Kraemer and Ratamess, 2004, Folland and Williams, 2007, Tan, 1999, ACSM, 2013).
However, BFR-RT studies have used a range of exercise intensities from 15% MVIC
(Kacin and Strazar, 2011) to approximately ~80% 1-RM (Laurentino et al., 2008, Cook
et al., 2013). Overall, the majority of protocols utilize an exercise load equal to 20% 1-
RM (Sumide et al., 2009, Takano et al., 2005, Cook et al., 2007, Yasuda et al., 2005,
Moritani et al., 1992, Kubo et al., 2006, Pierce et al., 2006, Wernbom et al., 2006,
Karabulut et al., 2010b, Abe et al., 2005b) and some using 30% 1-RM (Madarame et
al., 2008, Yasuda et al., 2006, Yasuda et al., 2010c, Loenneke et al., 2010a, Clark et al.,
2010, Madarame et al., 2010a, Yasuda et al., 2010b) as a means of increasing muscle
strength and mass. Light-load training (20-30% 1-RM) with BFR has repeatedly been
shown to improve muscle strength and mass, and is much lower than what was
previously thought to be required to induce these adaptations (Kraemer et al., 2002,
Kraemer and Ratamess, 2004, Folland and Williams, 2007, Tan, 1999, ACSM, 2013).
Until recently, it was not clear if training at higher workloads (i.e. ≥ 60% 1-RM) with
BFR would further enhance muscle strength and mass compared to the traditional light-
loads lifted during BFR-RT (i.e. 20-30% 1-RM). For example, elbow flexion training
with 50% 1-RM (Burgomaster et al., 2003), and knee extension training at 60 and 80%
1-RM (Laurentino et al., 2008) provided no additional benefit to muscle strength or

25
mass in comparison with non-BFR-RT at the same intensity. In contrast, Cook et al.,
(2013) found greater improvements in 1-RM strength for bench press and squat, sprint
times, and countermovement jump height following three weeks of training at 70% 1-
RM with BFR, compared with controls that trained with the same loads without BFR.
Interestingly, perhaps a more practical approach for resistance training programming in
healthy populations is to utilize BFR-RT in combination with HLRT (Yasuda et al.,
2010c, Yamanaka et al., 2012, Luebbers et al., 2014). For example, Yasuda et al.,
(2010d) divided participants into three training groups that completed six weeks of
bench press training. The three groups were HLRT (75% 1-RM), two training sessions
per week of BFR (30% 1-RM; 100-160 mmHg, 3 cm cuff width) in conjunction with
one session of HLRT without BFR, or BFR-RT three times per week. While all groups
increased maximal strength, pectoralis major and triceps brachii muscle CSA following
training, the gains were greater for HLRT (19.9, 17.6, and 8.6%, respectively) and the
combined BFR+HLRT group (15.3, 10.5, and 8.6%, respectively) compared with BFR-
RT alone (8.7, 8.3, and 4.9%, respectively). While the use of HLRT in conjunction with
BFR as part of the same periodised training programme may be beneficial for
adaptations in strength and hypertrophy for trained athletes and healthy individuals,
many “at risk” clinical populations may not often be recommended to perform HLRT.
Therefore, using loads of up to 50% 1-RM during BFR-RT would seem to be sufficient
to produce increases in muscle strength and mass, and perhaps would be more practical
and safe to use in clinical populations.
2.2.2.2 Exercise volume and rest periods
Resistance exercise/training volume is typically calculated one of two ways; (i) sets
multiplied by repetitions, or (ii) sets multiplied by repetitions multiplied by the
resistance exercise load (Kraemer et al., 2002, Kraemer and Ratamess, 2004, Folland

26
and Williams, 2007, Tan, 1999, ACSM 2013). The volume of resistance exercise
completed (and overall time under muscular tension (Tran et al., 2006)) during a
training programme is an important training variable for maximising gains in strength
and muscle mass (Kraemer et al., 2002, Kraemer and Ratamess, 2004, Folland and
Williams, 2007, Tan, 1999, ACSM, 2013). In the BFR literature it is problematic to
determine an optimal exercise volume for BFR-RT due to differences in training
durations, exercise selection, and BFR variables. Completing exercise to volitional
fatigue for all sets appears to be common (Takarada et al., 2000c, Takarada et al., 2002,
Cook et al., 2007, Kacin and Strazar, 2011, Wernbom et al., 2006, Nielsen et al., 2012,
Wernbom et al., 2009). However, this may not be recommended for “at risk” clinical
populations, untrained populations, or those with low levels of motivation. Therefore,
an alternative and more frequent set and repetition scheme used in the BFR-RE/RT
literature is one set of 30 repetitions followed by three sets of 15 repetitions for each
exercise, for a total of 75 repetitions (Madarame et al., 2008, Yasuda et al., 2010b,
Loenneke et al., 2010b, Wilson et al., 2013, Yasuda et al., 2012a, Yasuda et al., 2014b).
It would appear that doubling this set and repetition scheme (i.e. 150 repetitions total) is
not any more efficacious compared with the traditional method or HLRT (Martín‐
Hernández et al., 2013), indicating that there may a volume threshold over which
increases are not advantageous (Loenneke et al., 2011d, Martín‐Hernández et al., 2013).
In fact, several studies have shown beneficial adaptations to muscle strength and mass
following lower training volumes such as 3 sets of 15 repetitions (Sakuraba and
Ishikawa, 2009, Kim et al., 2009, Kim et al., 2012b, Karabulut et al., 2010a, Karabulut
et al., 2011a), which may suggest that the threshold may be much lower than previously
thought. Future research is needed to determine the optimal volume for producing
favourable increases in muscle strength and mass following BFR-RT.

27
The effect of inter-set rest periods is one acute training variable in the BFR literature
that has not received much attention, and is also often overlooked in the traditional
resistance training literature (Bird et al., 2005, Fleck and Kraemer, 1988). While longer
rest periods (i.e. 2-5 minutes) are required for maximal strength and power training
(Kraemer et al., 2002, Kraemer and Ratamess, 2004) due to the heavy demand placed
on the neuromuscular system, it would appear that in combination with the high levels
of volume during BFR-RE, that rest periods are short in duration. For example, a recent
meta-analysis found that 30 seconds of rest between sets produced greater strength
gains compared with 60 seconds of rest (Loenneke et al., 2011f). However, it was
acknowledged by the authors that every study utilizing 60 second rest periods was a
walking study (Abe et al., 2009, Beekley et al., 2005). While this is a serious limitation,
it would appear that for BFR-RE, short rest periods of 30-60 seconds are most
commonly prescribed in the literature, and meet the recommendations for hypertrophy
training (Kraemer et al., 2002, Kraemer and Ratamess, 2004, Bird et al., 2005).
2.2.2.3 Programme frequency and duration
Resistance training frequency is known to depend on a number of factors including
volume, intensity, exercise selection, training status, and training goals (Kraemer et al.,
2002). In order to develop maximal gains in muscle strength and mass following HLRT,
it is suggested that training should be conducted 2-4 times per week for each body
part/muscle group (Kraemer et al., 2002, Kraemer and Ratamess, 2004, Bird et al.,
2005). However, because BFR-RE/RT is performed using light-loads (i.e. 20-30% 1-
RM) the frequency of training may be higher compared with HLRT. Studies have
reported beneficial gains in muscle strength and mass following training twice per week
(Takarada et al., 2000c, Takarada et al., 2002, Madarame et al., 2008, Burgomaster et

28
al., 2003, Laurentino et al., 2008), and it is not uncommon for training to be conducted
twice daily (Yasuda et al., 2005, Abe et al., 2006, Ohta et al., 2003, Yasuda et al.,
2010b). While reported increases in DOMS may be a barrier to such high volume
training following BFR-RT (Umbel et al., 2009), higher training frequencies may allow
for a more rapid recovery following injury (Ohta et al., 2003, Loenneke et al., 2012a),
or attenuate losses in muscle function during prolonged bed rest due to inactivity,
illness, or disease (Takarada et al., 2000b, Kubota et al., 2010, Kubota et al., 2008a,
Cook et al., 2010).
The duration of the BFR-RT programme is also an important variable to consider, but
one that is not often acknowledged within the literature. Several studies have reported
significant increases in muscle strength and mass in as little as one (Abe et al., 2005a,
Abe et al., 2005b, Fujita et al., 2008b) and two weeks of training (Abe et al., 2005c,
Yasuda et al., 2005), with the gain in muscle mass being much more rapid than that
typically expected for traditional HLRT (Sale, 1988). Of note though, these studies
required high training frequencies and volumes of training up to twice daily. Most of
the literature has focussed on training adaptations following 3-6 weeks of training (Abe
et al., 2005c, Yasuda et al., 2005, Abe et al., 2005b, Clark et al., 2010, Cook et al.,
2013, Luebbers et al., 2014, Kriley, 2014), with few examining the neuromuscular,
haemodynamic, endocrine, and perceptual adaptations following training programs
equal to or greater than eight weeks (Moore et al., 2004, Burgomaster et al., 2003,
Laurentino et al., 2008, Laurentino et al., 2012, Kubo et al., 2006).

29
2.2.2.4 Mode of exercise
BFR has been combined with several types of resistance exercises and is most
commonly used during single joint, isolation exercises of the upper- (e.g. elbow flexion,
elbow extension) and lower-body (e.g. knee extension, knee flexion, calf raise). While
these specific muscles can be easily isolated during resistance exercise/training, a
number of compound exercises such as the squat (Abe et al., 2005c, Yasuda et al., 2005,
Abe et al., 2005b, Item et al., 2011) and bench press (Yasuda et al., 2006, Yasuda et al.,
2008, Yasuda et al., 2010b) have also been performed with BFR. Indeed, changes in
both muscle strength and size can be observed in the non-restricted trunk musculature
following training (Yasuda et al., 2006, Yasuda et al., 2008, Yasuda et al., 2010b).
While this information is important, single exercise training programs may not replicate
“real world” resistance training programmes which are composed of one or more
exercises for each body part that make up a full-body resistance training programme in
order to enhance physical and functional ability (Gordon, 2009, Fleck and Kraemer,
2014). Several recent BFR-RT studies have completed multiple lower- (Kim et al.,
2009, Loenneke et al., 2012g, Karabulut et al., 2010a) and upper-body (Weatherholt et
al., 2012, Thiebaud et al., 2013a) resistance exercises as part of a training programme
and show favourable increases in both muscle strength and mass. Therefore, it should
also be expected that a full-body BFR-RT programme incorporating both upper- and
lower-body exercises which replicate “real world” application, would also be largely
beneficial regarding the development of muscular strength and mass, however, this is
yet to be investigated.
Additionally, BFR has been applied to investigate the adaptation of skeletal muscle
following cycling (Ozaki et al., 2010, Corvino et al., 2014), swimming (Abdelfattah
and Salem, 2011), body weight circuit training (Ishii et al., 2005), and whole body

30
vibration training (Toigo et al., 2010, Item et al., 2011). Another common exercise
modality is combining BFR during walk training (Abe et al., 2006, Abe et al., 2009,
Abe et al., 2010). Briefly, this exercise involves applying continuous BFR (160-240
mmHg) to the proximal portion of both thighs for five sets of two minute bouts
interspersed with one minute rest periods. While no changes in strength or muscle
mass have been found in the control walk groups, muscle strength and mass have
been shown to increase by as much as 8% following short duration training (3-6
weeks) (Abe et al., 2006, Abe et al., 2009, Abe et al., 2010). Based on these and other
findings, while the combination of BFR with different modes of exercise during
training may increase muscle strength and mass, as well as improve overall health,
further research is needed to support these claims and to clarify the magnitude these
of gains from BFR in all types of exercise training.
2.2.2.5 Safety considerations
Although previous literature has established the efficacy of BFR exercise with respect
to muscular strength and mass, optimal methods for its application have not yet been
identified, and therefore, the practicality and safety of its use have been investigated
(Loenneke et al., 2011b, Manini and Clark, 2009, Wernbom et al., 2008).
One of the main criticisms of BFR exercise is that even though light-loads are utilized,
ratings of pain and perceived exertion (RPE) may be very high during exercise in
comparison with exercise of the same intensity without BFR (Hollander et al., 2010,
Loenneke et al., 2010a, Wernbom et al., 2006, Wernbom et al., 2009, Vieira et al.,
2014, Fitschen et al., 2013, Rossow et al., 2012). It should be noted that in the study by
Wernbom et al., (2006) wide cuffs were used, and in a more recent comparison by
Rossow et al., (2012) it was found that subjects rating of pain and perceived exertion

31
are higher with wide cuffs in comparison with narrow cuffs when using the same
restriction pressures. Although extensive research has compared perceptual responses
between BFR-RE and load matched controls, less is known about the effects in
comparison with traditional HLRT. One study reported RPE to be similar between
elbow flexion BFR-RE and HLRE (Hollander et al., 2010), while a more recent study of
the same muscle group observed higher RPEs following BFR-RE (Vieira et al., 2014).
Therefore, with limited evidence it is difficult to make any clear recommendations, but
considering that many favourable adaptations that occur with BFR-RT are similar to
HLRT, but with lighter-loads, then perhaps it may be expected that RPE and pain is at
least not any greater than HLRT. One reason that may be responsible for the increase in
discomfort and pain ratings in some studies is reportedly due to the use of high
restrictive cuff pressures (≥ 250 mmHg), which effectively causes complete arterial
occlusion (Loenneke et al., 2010a, Karabulut et al., 2011b, Cook et al., 2007, Sumide et
al., 2009) and prevents completion of a full exercise bout (Yasuda et al., 2009).
Secondly, injuries to the soft tissue beneath a tourniquet have been shown to have a
direct relationship with the applied pressures, and since high pressures may induce
injury more rapidly, the lowest possible pressure that achieves beneficial results should
be used (Shaw and Murray, 1982). Finally, although BFR-RE/RT involves light-loads,
perhaps the relatively high exercise volumes (e.g. total of 75 repetitions, or exercise sets
to muscular failure) is another reason for the increased RPE and pain responses during
exercise.
In addition to the acute increase in RPE and pain during exercise, DOMS has also been
observed following BFR-RE. DOMS typically occurs following an unaccustomed
exercise bout, or due to higher than expected increases in exercise intensity (i.e. load
lifted) or volume (Cheung et al., 2003, Connolly et al., 2003, McHugh, 2003). DOMS is

32
usually manifested within 8-12 hours post-exercise, and peaks between 24 and 72 hours
post-exercise before returning to resting levels within 7-10 days (Cheung et al., 2003,
Clarkson et al., 1992, Armstrong, 1984). For BFR-RE, two sets of isotonic knee
extension exercise (35% MVIC) with BFR (130% of systolic blood pressure) induced
significant elevations in muscle soreness ratings at 24 and 48 hours post-exercise before
returning to baseline at 96 hours (Umbel et al., 2009). In agreement with this, Wernbom
et al., (2006a, 2009) found that DOMS was significantly elevated following BFR knee
extension exercise at various loads (20-50% 1 RM). Furthermore, results from these
studies show that the DOMS response following BFR-RE is greater than LLRE
(Wernbom et al., 2006, Wernbom et al., 2009, Umbel et al., 2009). However, the
question remains as to whether BFR induced DOMS is different in comparison with
HLRE.
Despite the increased levels of perceptual responses during BFR-RE, one appealing
aspect is that there appears to be no prolonged increase in muscle damage such as
muscle inflammation and swelling, decreased force production, and increased blood
markers measuring muscle damage such as creatine kinase and myoglobin levels
(Thiebaud et al., 2013b, Karabulut et al., 2013, Loenneke et al., 2014a, Wilson et al.,
2013). One previous study observed that changes in muscle swelling, circumference,
and range of motion returned to baseline within 24 hours following BFR elbow flexion
exercise (Thiebaud et al., 2013b). Moreover, using elastic wraps to induce BFR has
been shown to acutely increase muscle swelling, but this subsided within 10 mins and
had no negative effects on perceptual responses post-exercise (Wilson et al., 2013).
Furthermore, BFR-RE has not been shown to alter circulating creatine kinase (Abe et
al., 2006, Takarada et al., 2000a), myoglobin content (Abe et al., 2006), or
inflammatory markers such as interleukin-6 (Karabulut et al., 2013). Alarmingly

33
though, one case study report has found significant sustained elevations in creatine
kinase following a single BFR knee extension exercise bout (100 mmHg, 14 cm wide
cuff) that lead to rhabdomyolysis (Iversen and Røstad, 2010). However, the patient was
discharged from hospital after three days, and 18 days after the incident returned to
BFR-RE. While this is the first report of rhabdomyolysis associated with BFR-RE/RT,
in a risk assessment survey of BFR-RT in Japan, this complication was reported to have
an incidence rate of 0.008%, but no further details were presented (Nakajima et al.,
2006). This information supports the notion that BFR-RE does not induce significant
levels of muscle damage, despite some studies demonstrating decrements in maximal
voluntary contraction immediately post exercise (Loenneke et al., 2012d), and at 24
hours post exercise (Umbel et al., 2009, Wernbom et al., 2012a). Importantly though, it
has been shown that DOMS and pain subsides after a few exercise sessions (Fitschen et
al., 2013) that suggests a protective repeated bout effect (McHugh, 2003, Nosaka and
Clarkson, 1995), which may also be a contributing factor to the increases in muscle
mass associated with BFR-RT (Thiebaud, 2012, Schoenfeld, 2012).
Other side effects that have been reported during BFR exercise include reduced
peripheral sensation, dizziness, and fainting (Ohta et al., 2003, Sumide et al., 2009,
Nakajima et al., 2006). Further to this, in a comprehensive survey of approximately
13,000 participants that have received Kaatsu training in Japan, only a small number of
complications were reported (Nakajima et al., 2006). The most frequent side effects
reported were subcutaneous haemorrhage (13.1%) and temporary numbness (1.2%),
whilst cerebral anaemia, cold feeling, venous thrombus, pulmonary embolism, pain, a
rise in blood pressure, and fainting all had an incidence rate of less than 1% (Nakajima
et al., 2006). Although the incident rate of thrombosis was low in this survey (and was
not compared to a control condition, or natural incidence rate for the given population),

34
it is likely that thrombolytic events is one of the more common safety concerns with
respect to BFR exercise (Wernbom et al., 2008, Loenneke et al., 2011b, Mattar et al.,
2014). Preliminary analysis suggests that BFR-RE/RT does not result in blood clotting
or decrements in vascular function when conducted in a controlled environment and
when monitored by experienced personnel. However, due to the alterations in normal
blood flow, it seems reasonable that thrombolytic events should still be of some concern
for some susceptible populations. In addition, BFR exercise has been observed to
increase cardiovascular stress greater than LLRE without BFR (for review the reader is
directed to section 2.5, page 76), such as increased heart rate, blood pressure, and
cardiac output, while stroke volume has been shown to decrease due to reductions in
venous return (Takano et al., 2005). Based on this evidence, it would seem that BFR
exercise should be prescribed carefully in participants with cardiac diseases such as
ischemic heart diseases, hypertrophic cardiomyopathy, and participants with
hypertension (Nakajima et al., 2006). As an example, it would seem many research
facilities, health practitioners, and sporting institutes will screen participants for blood
clotting conditions (e.g. blood and platelet count, family history of thrombosis or
disease affecting the vasculature, smoking habits) as this would increase the risk of
thrombolytic events occurring.
Despite the mounting evidence for the general efficacy of BFR exercise in healthy
young populations, there have been fewer implementations of BFR in the elderly (Ozaki
et al., 2011a, Abe et al., 2010, Fry et al., 2010, Takarada et al., 2000c, Sakamaki et al.,
2008) and “at risk” clinical populations where this training modality may perhaps be
most beneficial. Due to the inherent nature of research institutes generally being within
universities, a large majority of the current research completed has been performed in
young and/or healthy populations, and it is possible that BFR-RE/RT may have higher

35
risks in populations with comorbidities. In general, the primary concerns regarding BFR
exercise are those associated with training induced alterations in; (i) adverse
cardiovascular responses (Takano et al., 2005, Kacin and Strazar, 2011, Sakamaki et al.,
2008); (ii) blood clotting and vascular function (Clark et al., 2010, Fry et al., 2010); and
(iii) nerve and muscle damage (Clark et al., 2010, Manini and Clark, 2009, Umbel et al.,
2009). While the current research on BFR-RE/RT with respect to these safety outcomes
is encouraging, further research needs to be completed in both healthy and clinical
populations to better determine under what conditions BFR-RE/RT can be safely used.
2.2.3 Summary
The majority of literature investigating BFR-RE/RT (and other modes of exercise)
indicates promising prospects as an alternative to HLRT to enhance muscle strength,
mass and clinical rehabilitation outcomes in populations with limited resistance training
capacity. Currently, evidence suggests that BFR-RE/RT provides a safe training
alternative for most individuals regardless of age and training status when used in a
controlled environment and monitored by experienced personnel. Therefore, from the
available literature, and in agreement with reviews by Fahs et al., (2012) and Scott et
al., (2014) it is recommended that:
i. The restrictive cuff pressure should be individualized according to each
participant’s systolic blood pressure, limb circumference, or resting arterial LOP
to ensure only partial occlusion (i.e. 50-80% LOP).
ii. In addition, wider cuffs (e.g. 12-14 cm for the lower-body and 8-10 cm for the
upper-body) may be preferred compared with narrow cuffs (e.g. 5 cm for the
lower-body and 3 cm for the upper-body) due to the lower restrictive pressures.
iii. Both continuous and intermittent BFR may result in beneficial adaptations to
muscle strength, mass, and endurance.
iv. An exercise load of 20-30% 1-RM is adequate to induce significant adaptations
in muscle strength, mass, and endurance.

36
v. The traditional set x repetition scheme of 30/15/15/15 may be the preferred
method prescribed during BFR-RE/RT, although lower training volumes
(particularly when starting a training program) will also result in beneficial
muscular adaptations while potentially reducing the effects of DOMS and high
RPE and pain.
vi. Training twice daily with BFR may accelerate increases in muscle strength and
mass; however, training 2-3 days per week per muscle group appears to be an
adequate training frequency.
vii. BFR can be applied during single (e.g. elbow flexion/extension, knee
flexion/extension) or multi-joint (e.g. squat, bench press) resistance exercises to
increase muscle strength, mass, and endurance.

37
2.3 Training adaptations
Resistance exercise/training is one of the most widely practiced forms of physical
activity that is used to increase musculoskeletal health, counteract muscle weakness
disorders (e.g. sarcopenia, neuromuscular diseases, or following injury), enhance
athletic performance, and alter body aesthetics (Folland and Williams, 2007). Increases
in muscle strength, mass, and endurance following HLRT and BFR-RT are already well
established, and while the underlying stimuli are generally well understood for HLRT,
the same cannot be said for BFR-RT. The mechanisms underlying adaptations to
strength are reviewed extensively in section 2.4 (pages 57-75); while mechanisms
underlying adaptations to muscle hypertrophy are reviewed in section 2.3.2 (pages 46-
52).
The following will review the training adaptations with respect to both HLRT and BFR-
RT. Comparisons with HLRT are not only important in order to understand the
potential gains in muscle strength, mass, endurance, and the driving mechanisms behind
BFR-RT, but also to evaluate BFR-RT as a potential “low-risk” alternative to HLRT.
Clearly, HLRT is the most well proven technique for developing muscle strength and
mass (for review see Semmler and Enoka (2000), and Folland and Williams (2007)),
however, in some instances (e.g. following musculoskeletal injury, during
immobilization and bed rest, and for weak or frail individuals due to inactivity or
disease) may only be cautiously prescribed despite potential benefits to reduce muscle
atrophy and improve functional capacity. Therefore, to induce strength and hypertrophy
with minimal risk to health and injury, BFR-RT should be of special interest.

38
2.3.1 Muscle strength and mass
It is generally accepted that the initial increase in strength that occurs during the first
four weeks of HLRT is driven by neural adaptations that are not accompanied by
proportional increases in muscle hypertrophy (Folland and Williams, 2007, Moritani
and DeVries, 1979, Sale, 1988). For example, Kidgell et al. (2010) showed that
following four weeks of HLRT of the elbow flexors (4 sets of 6-8 repetitions at 80% 1-
RM), 1-RM strength increased significantly by 28% in the absence of muscle
hypertrophy. However, when HLRT is conducted over more prolonged periods (≥ 6
weeks) the further gain in strength is driven more by morphological adaptations such as
hypertrophy and/or hyperplasia, with little further adaptation in neural mechanisms
(Abe et al., 2000, Moritani and DeVries, 1979, Narici et al., 1996, Sale, 1988). The
classic curve developed by Sale (1988) shows the theoretical interaction of neural
mechanisms with muscle fibre hypertrophy and is presented in Figure 2.1.
Figure 2.1 The theoretical interplay of the neural factors and hypertrophy factors over time with
resistance training (Sale, 1988).

39
While HLRT is typically recommended to induce the greatest increase in maximal
strength and muscle hypertrophy (Kraemer et al., 2002, Kraemer and Ratamess, 2004,
Folland and Williams, 2007, Tan, 1999, ACSM, 2013), recent evidence suggests that
BFR-RT may produce similar gains (Karabulut et al., 2010a, Karabulut et al., 2011a,
Martín‐Hernández et al., 2013, Thiebaud et al., 2013a, Karabulut et al., 2013, Lowery et
al., 2013, Clark et al., 2010, Takarada et al., 2000c, Kim et al., 2009, Laurentino et al.,
2012), and these adaptations have also been shown to be significantly greater when
compared with LLRT without BFR (Abe et al., 2005a, Abe et al., 2005b, Abe et al.,
2005c, Shinohara et al., 1998, Takarada et al., 2002, Takarada et al., 2000c, Takarada et
al., 2004, Yasuda et al., 2005, Yasuda et al., 2010b). To date, few studies have
compared the effects of all three training protocols (HLRT, LLRT, and BFR-RT) on
strength and hypertrophy (Takarada et al., 2000c, Laurentino et al., 2012, Fahs et al.,
2011a). In a seminal study completed by Takarada et al., (2000c), untrained participants
completed three sets of unilateral elbow flexion exercise until muscular failure under
the following conditions; 80% 1-RM, ~40% 1-RM without BFR, and ~40% 1-RM with
BFR (~110 mmHg). The percent change in isokinetic strength following BFR-RT was
significantly greater than LLRT (18.4 ± 1.5% versus 1.04 ± 1.2%), and similar to HLRT
(22.6 ± 2.0%). In addition, biceps brachii CSA increased by 18.4 and 20.3% following
HLRT and BFR-RT, respectively, which were significantly larger than LLRT (6.9%).
Unfortunately, by using only one group of subjects that completed BFR-RT with one
arm (~40% 1-RM), while completing HLRT simultaneously with the contralateral arm
(80% 1-RM), this study design questions the source of improvements in muscle strength
given that strong voluntary contractions of a single limb are associated with increases in
neural drive to the untrained limb (Zijdewind et al., 2006). Furthermore, the gain in
strength following unilateral HLRT (Goodwill et al., 2012, Hortobyagi et al., 1997,
Kidgell and Pearce, 2009, Munn et al., 2004) also produces gains in strength of the

40
contralateral untrained limb (termed ‘cross education’) (Munn et al., 2004, Hendy et al.,
2011). More recently, Laurentino et al., (2012) observed that eight weeks of knee
extension resistance training significantly increased 1-RM strength for both HLRT
(36.2%) and BFR (40.1%), with the gains being greater than LLRT (20.7%). However,
the change in quadriceps CSA was not different between groups.
2.3.1.1 Short-term training (2-6 weeks)
Brief training periods of less than four weeks have resulted in gains in both muscle
strength and mass for both HLRT and BFR-RT. For example, while the same
magnitude of strength increase (~10%) was observed following four weeks of knee
extension training (Clark et al., 2010), when two additional lower-body exercises were
added to a three week training program, both the percent change in muscle strength
(~17 versus ~30%) (Kim et al., 2009) and CSA (1.15 ± 0.54 versus 3.48 ± 0.68%) (Kim
et al., 2012b) were shown to be greater (approximately double) following HLRT
compared with BFR. Two further studies (Yasuda et al., 2011, Yasuda et al., 2010c)
observed that the gains in bench press 1-RM strength following six weeks of BFR-RT
to be approximately half that achieved with HLRT in untrained participants. In a series
of studies from what appears to be the same sample population and study design
(Karabulut et al., 2010a, Karabulut et al., 2011a, Karabulut et al., 2013), participants
completed leg press and knee extension training three times per week for six weeks
with either heavy-loads (80% 1-RM) or light-loads with BFR (20% 1-RM; Kaatsu
Master, 205.4 ± 4.3 mmHg). Interestingly, the percent change in 1-RM knee extension
strength was significantly greater for HLRT (31.2%) compared with BFR (19.1%), but
the percent change in 1-RM leg press strength was similar (~20%). Furthermore,
muscle CSA measured via peripheral quantitative computed tomography (pQCT),

41
increased by ~1.3-3.7% but was not different between HLRT, BFR-RT and a non-
training control group.
While HLRT may not be recommended to some clinical populations with limited
strength capacities, BFR-RT with light-loads provides a potential alternative that, when
matched for the same volume and intensity of training, is generally shown to be a
superior method for increasing muscle strength and mass when compared with LLRT
without BFR (Abe et al., 2005a, Abe et al., 2005b, Abe et al., 2005c, Shinohara et al.,
1998, Takarada et al., 2002, Takarada et al., 2000c, Takarada et al., 2004, Yasuda et al.,
2005, Yasuda et al., 2010b). As mentioned previously, several studies have reported
significant increases in muscle strength and mass in as little as one (Abe et al., 2005a,
Abe et al., 2005b, Fujita et al., 2008b) and two weeks of BFR-RT (Abe et al., 2005c,
Yasuda et al., 2005), with no changes observed following LLRT. While the increase in
muscular strength within these short periods of training is well known following
traditional HLRT, the significant increase in muscle mass appear more rapid than what
would typically be expected (e.g. see Figure 2.1) (Sale, 1988), and as such should
possibly be viewed with caution. For example, the relatively rapid hypertrophic
responses observed in these studies may be due to increased cellular swelling associated
with the BFR technique (Loenneke et al., 2012b, Ogawa et al., 2012, Thiebaud et al.,
2013b, Wilson et al., 2013, Yasuda et al., 2010a, Yasuda et al., 2008, Yasuda et al.,
2012b) rather than an accumulation of contractile protein resulting from an increase in
protein synthesis/decreased protein degradation. However, several studies have shown
that the muscle/cell swelling decreases after several hours (Wilson et al., 2013,
Thiebaud et al., 2013b) and may in fact play a role in activating molecular signalling
pathways such as Akt/mTOR that are responsible for increasing protein synthesis
(Loenneke et al., 2011a). Of importance, some studies have controlled for the
muscle/cell swelling phenomenon as well as inflammatory markers, and not only

42
measured the change in muscle mass immediately post a BFR-RT programme, but also
two to ten days post-training (Fujita et al., 2008b, Abe et al., 2005a, Farup et al., 2015).
These short-term studies have shown that muscle CSA remains elevated above pre-
training levels by up to 3-5%, as well as resulting in concurrent increases in strength.
For example, Yasuda et al., (2005) showed a 14% increase in 1-RM squat strength
following two weeks of BFR-RT, as well as a 5.9% and 27.6% in type I and type II
muscle fibre size. In light of these examples, it appears that sarcoplasmic hypertrophy is
probably not playing a role in the sustained elevated responses in muscle CSA.
Therefore, while the stimuli underlying hypertrophic adaptations to BFR-RT still
require further research (see section 2.3.2, pages 46 – 52), from the available evidence it
does appear that BFR-RT can result in early gains in muscle mass.
2.3.1.2 Longer-term training (> 6 weeks)
Further studies have examined changes in muscle strength and mass following longer
training durations (≥ six weeks) and observed similar increases in muscle strength and
mass between groups in the upper-body (Thiebaud et al., 2013a, Takarada et al., 2000c)
and lower-body (Ellefsen et al., 2015) in untrained populations. When the duration of
training is further extended for highly trained athletes, eight weeks of bilateral knee
extension training with BFR resulted in a 14% increase strength and increased
quadriceps CSA by 15% (Takarada et al., 2002). These changes were significantly
greater than LLRT (3.2% for strength; data not shown for CSA) However, in contrast to
these findings, Burgomaster et al., (2003) demonstrated similar increases between BFR-
RT and LLRT in maximal strength following eight weeks of unilateral elbow flexion
exercise in untrained healthy males (10.5% and 9.6% increase for BFR-RT and LLRT,
respectively). However, this result is potentially confounded with the higher than usual
loads utilized during the training program (50% 1-RM). Additionally, several studies

43
have shown similar increases in muscle strength and mass occur between BFR-RT and
LLRT when the exercise is completed to muscular failure (Kacin and Strazar, 2011,
Farup et al., 2015), which is not surprising given the importance of increased training
volume and fatigue in the development of these adaptations (Rooney et al., 1994,
Schoenfeld, 2013, Schoenfeld et al., 2015). However, it is important to note that
although both BFR-RT and LLRT to muscular failure result in similar increases in
muscle strength and size, this is achieved at lower exercise volumes for BFR-RT due to
the increased rate of muscle fatigue elicited (Kacin and Strazar, 2011, Karabulut et al.,
2010b, Fujita et al., 2008a).
It is very difficult to compare results of the aforementioned data throughout this section,
as the type of training employed (i.e. muscles trained, mode of exercise, frequency,
duration, rest intervals, and intensity) and the conditions in which BFR was applied
were different between studies. In addition, the training status of the majority of studies
has focussed on untrained populations and much less is known about the adaptations in
trained participants. However, from the data described above, it appears that while
HLRT may still provide the greatest stimulus to gain muscle strength and mass, BFR-
RT is a superior training method compared to LLRT (not to failure). As mentioned
previously, this type of training has important implications for populations with limited
resistance training capacities. Therefore, future studies should compare the effects of all
three training interventions (HLRT, LLRT, and BFR-RT) on strength and hypertrophy
to improve our understanding of the potential benefits of BFR-RT in comparison with
traditional resistance training methods.

44
2.3.1.1 De-training
While the chronic muscular adaptations (i.e. muscle strength and hypertrophy) to BFR-
RT have been characterised (Loenneke et al., 2011f, Pope et al., 2013, Scott et al., 2014,
Wernbom et al., 2008), research investigating how well participants retain these
adaptations following a period of de-training is limited (Yasuda et al., 2014a, Yasuda et
al., 2014b, Yasuda et al., 2014c, Yasuda et al., 2015). Traditionally, it is expected that
muscle strength and mass progressively decrease with long-term de-training (Narici et
al., 1989, Hakkinen et al., 2000), but in some instances these gains can still be preserved
higher than baseline levels (Lemmer et al., 2000, Staron et al., 1991, Andersen et al.,
2005).
For BFR-RT, only four recent studies have attempted to measure muscle strength and
mass following a period of de-training, all by the same primary investigator (Yasuda et
al., 2014a, Yasuda et al., 2014b, Yasuda et al., 2014c, Yasuda et al., 2015). In one
example, six weeks of bench press exercise produced significant increases in 1-RM
strength as well as increased triceps brachii and pectoralis major CSA for both HLRT
and BFR-RT (Yasuda et al., 2014b). Following three weeks of de-training, 1-RM
strength remained elevated for both HLRT and BFR-RT, but triceps brachii and
pectoralis major CSA only remained elevated for the HLRT group. Both 1-RM strength
and muscle mass remained higher for HLRT compared with BFR-RT, and these
differences were probably because the gain in strength and mass were greater for HLRT
during the training period. Similarly, following six weeks of elbow flexion training with
BFR (Yasuda et al., 2014c), isometric strength as well as MRI-measured CSA were
shown to increase in young men that completed a concentric only BFR-RT (there were
no changes following eccentric BFR-RT). After a six week de-training period, both
MVC strength and biceps brachii CSA remained significantly higher than pre-training
levels for concentric only BFR-RT, which were also similar to the post-training levels.

45
Finally, in another study by Yasuda et al., (2014a), changes in muscle strength and mass
were investigated following 12 weeks of knee extension and leg press with BFR or
LLRT without BFR in older adults (~70 years). Maximal 1-RM strength for both
exercises was shown to be significantly increased following BFR-RT (~21-26%), and
while 1-RM strength was lower than the post-training time-point, it remained
significantly elevated compared with baseline levels after 24 weeks of de-training (9-
15%). A similar pattern was observed for quadriceps CSA as measured by MRI
following training (7% increase), but this returned to baseline levels following the de-
training period. No change in muscle strength or mass was seen following LLRT, and
the de-training period resulted in similar values compared with pre- and post-training.
While the mechanisms remain speculative, the retention of muscle strength in both
young and older adults above baseline levels seen in these studies (and also following
de-training periods after HLRT) of both short- and long-term de-training periods, it is
probably due to neural adaptations such as increased muscle activation (motor unit
recruitment). However, neural adaptations following de-training have not been
measured in the BFR-RT literature. Regarding the loss in muscle mass following short-
(three weeks) and long-term (24 weeks) de-training periods, it is expected that the
major signalling pathways responsible for protein synthesis regulation are effectively
down regulated during de-training, resulting in an overall reduction in muscle protein
synthesis and muscle loss. The reader is directed to section 2.3.2 (below) for more
information regarding the molecular signalling pathways involved with BFR-RE/RT.
While this seems plausible, future work is required to be able to explain the exact
physiological mechanisms involved during de-training following BFR-RT. In addition,
it remains to be seen how well strength and muscle mass is retained during de-training

46
following a full-body BFR-RT programme which may be more representative of “real
world” application of its use.
2.3.2 Mechanisms underlying hypertrophy
The mechanisms underlying the gain in muscle mass observed following BFR-RT
remain speculative, although they likely depend on a number of local and systemic
growth factors that work together to result in a net gain in muscle protein synthesis and
cell growth (Figure 2.2). In addition, with the available evidence it is currently
unknown if BFR-RT predominately results in myofibrillar or sarcoplasmic hypertrophy,
although both are known to occur following HLRT. While some of these findings
regarding mechanisms/stimuli relating to muscle hypertrophy following BFR-RT are
discussed below, it should be noted that these are not the focus of the current thesis. For
further discussion on these proposed mechanisms the reader is directed to reviews by
Manini and Clarke (2009), Loenneke et al. (2010b), Wernbom et al. (2008b), Pope et al.
(2013a), and Pearson et al. (2014).
Some of the proposed stimuli that are associated with the adaptations in muscle
hypertrophy following BFR-RT include;
i. Muscle fibre recruitment (see section 2.4.3, page 66 for further information on
neural responses): Despite the use of light-loads, evidence has demonstrated that
during BFR-RE there is an increase in muscle activity (via EMG) to levels greater
than LLRE without BFR (Moritani et al., 1992, Yasuda et al., 2006), and in some
instances similar to HLRE (Takarada et al., 2000c, Yasuda et al., 2008). The
increase in muscle activity observed has been suggested to be due to an increased

47
hypoxic-metabolic intramuscular environment (see points ii and iii, below),
resulting in the recruitment of high threshold motor units and their associated fast-
twitch muscle fibres in order to maintain force and protect against conduction
failure (Yasuda et al., 2010a). It would seem that simply applying and inflating
restrictive cuffs around the limb (in the absence of exercise) does not result in an
increase muscle activity. Therefore, it is the added BFR stimulus during exercise
that alters the pattern of motor unit recruitment, most likely due to an increase in
feedback from group III and IV muscle afferents (Yasuda et al., 2010a).
Recruitment of type II muscle fibres has also been confirmed by Suga et al., (2012)
who showed that both BFR-RE and HLRE result in similar split inorganic
phosphate (Pi) peaks via P-magnetic resonance spectroscopy (representing fast-
twitch fibre recruitment), however more recent work by Okita and Takada (2013)
reported contrasting results. This information is important, considering that
activation of fast-twitch muscle fibres have a greater hypertrophic potential
compared with slow-twitch muscle fibres, however, other factors relating to the
BFR stimulus are also likely to play a role.
ii. Decreased availability of oxygen: Due to the decrease in blood flow experienced
during BFR (at rest and during exercise) there is also a concomitant decrease in
muscle oxygenation levels. For example, using near-infrared spectroscopy, Ganesan
et al., (2014) observed a 7.5-11.2% reduction in vastus medialis oxygenation during
BFR knee extension exercise at 50% 1-RM. While the induced hypoxia observed
during BFR-RE is not an anabolic stimulus per se, it does seem to have an additive
effect on hypertrophy. Hypoxia induced during BFR-RE has been shown to increase
lactate accumulation and reduce lactate clearance rates (see point iii, below), which
may in turn increase muscle/cell swelling (see point v, below) and mediate

48
elevations in anabolic endocrine hormones and growth factors to activate satellite
cells, resulting in proliferation and muscle growth (Vierck et al., 2000).
iii. Metabolic responses: Large elevations in metabolic accumulation or an increase in
“metabolic stress” (possibly as a response to exaggerated ischemic-hypoxic
environments) is suggested to be a key stimulator for adaptations in muscle
hypertrophy following BFR-RT. Following acute bouts of BFR-RE, several studies
have observed exaggerated depletions of phosphocreatine stores (PCr) (Suga et al.,
2009, Okita and Takada, 2013), decreased intramuscular pH (Suga et al., 2009,
Suga et al., 2012, Okita and Takada, 2013), increased Pi (Suga et al., 2012) and
blood lactate (Fujita et al., 2007, Reeves et al., 2006, Takano et al., 2005, Takarada
et al., 2000a). These changes are greater when compared with LLRE (Fujita et al.,
2007, Suga et al., 2009, Takano et al., 2005, Takarada et al., 2000a), and in some
cases are similar to HLRE (Reeves et al., 2006, Suga et al., 2012). Furthermore, an
increase in muscle mass following two and four weeks of BFR-RT has been
correlated with various indicators of metabolic stress (e.g. changes in Pi and pH)
(Takada et al., 2012). In addition, Burgomaster et al., (2003) also reported
reductions in resting adenosine triphosphate (ATP) and increased muscle glycogen
stores following eight weeks of BFR-RT, most likely due to alterations in glucose
transport (GLUT-4 translocation) and glycogen synthase activity as a result of the
reduction in oxygen availability (Cartee et al., 1991). It is also expected that the
increased metabolic accumulation during BFR-RE is likely to facilitate other
physiological mechanisms responsible for muscle hypertrophy.
iv. Endocrine responses: Several early BFR studies reported exaggerated increases in
acute systemic hormonal responses such as growth hormone and insulin-like growth
factor-1 (Takano et al., 2005, Pierce et al., 2006, Takarada et al., 2000a). These are
typically higher than the increases seen following a typical bout of HLRE (Bottaro

49
et al., 2009, Kraemer et al., 1990, Linnamo et al., 2005). For example, one study
showed a 290-fold increase in growth hormone response following BFR-RE
(Takarada et al., 2000a), which is reported to be 1.7 times greater than changes seen
following HLRE (Kraemer et al., 1990). However, it is important to note that no
direct comparisons have been made between BFR-RE and HLRE. The increase in
growth hormone released may be due to increases in lactate and changes in acid-
base balance (Godfrey et al., 2003). While the role that acute systemic hormonal
responses play in inducing adaptations in muscle mass following resistance training
has recently been questioned (Rennie, 2003, West and Phillips, 2010), it has
nevertheless been hypothesised as a primary mechanism responsible for muscle
hypertrophy following BFR-RT. Other studies have examined the effect of BFR-RE
on responses in testosterone (Fujita et al., 2007, Madarame et al., 2010b, Reeves et
al., 2006) and cortisol (Reeves et al., 2006) with contrasting results. In general,
while BFR-RE promotes some favourable anabolic endocrine responses, the
evidence is limited; therefore other factors may play a greater role in the
hypertrophic responses seen following BFR-RT.
v. Cell swelling: An increase in intracellular hydration, reactive hyperaemia, or “cell
swelling” following the deflation or removal of the BFR pressure cuffs is one of the
more novel theories to be suggested responsible for growth in muscle size following
BFR-RT. This phenomenon was first described by Häussinger et al., (1993)
regarding HLRT, and more recently by Loenneke et al., (2011a, 2014b) in order to
explain the beneficial muscular adaptations that occur when BFR is applied in the
absence of metabolic accumulation (Loenneke et al., 2012e), hormonal responses
(Pierce et al., 2006), or changes in muscle activity. Following the removal of the
external BFR pressure cuff, several studies have observed immediate increases in
muscle size (e.g. as measured using ultrasonography), even in the absence of an

50
exercise intervention (Loenneke et al., 2012b, Ogawa et al., 2012, Thiebaud et al.,
2013b, Wilson et al., 2013, Yasuda et al., 2010a, Yasuda et al., 2008, Yasuda et al.,
2012b). It has been hypothesised that an intrinsic volume sensor detects the increase
in intracellular swelling, thereby activating molecular pathways (see point vi,
below) such as mammalian target of rapamycin (mTOR) and mitogen-activated
protein-kinase (MAPK) which may promote tissue growth via increased protein
synthesis. While this may indeed be a possible mechanism to explain the beneficial
adaptations in hypertrophy seen following BFR-RT, it is important to note that this
is currently just a hypothesis and has not been directly examined.
vi. Activation of molecular signalling pathways: It is possible that the above factors
observed during/following BFR-RE/RT play a role in the activation of subsequent
downstream molecular pathways within muscle that ultimately shift muscle protein
balance to favour synthesis over degradation. The Akt/mTOR pathway is believed
to be the main regulator of hypertrophy in muscle tissue and has been shown to
increase acutely following BFR-RE. For example, both Fujita et al., (2007) and Fry
et al., (2010) observed increases in phosphorylation of ribosomal S6 kinase 1
(S6K1; a key downstream regulator of the mTOR signalling pathway) as well as
increased muscle protein synthesis (MPS) three hours post-knee extension exercise
with BFR, but no change following non-BFR LLRE. While the enhanced mTOR
signalling observed following BFR-RE may play a crucial role for hypertrophic
adaptations following short- and long-term BFR-RT, further research is needed to
determine the relative contribution of this pathway in comparison with other
possible mechanisms, as well as in comparison with the acute and chronic responses
following HLRE/RT. An increase in the number of visible satellite cells is another
potential hypertrophic signalling stimulus that has received recent attention.
Satellite cell proliferation has been shown to be significantly elevated acutely

51
following BFR-RE (Wernbom et al., 2013), and also following short-term (eight
days) of training in addition to an increased number of myonuclei per myofibre
(Nielsen et al., 2012). Another mechanism that has been examined following BFR-
RE to explain adaptations in muscle hypertrophy is the production of reactive
oxygen species (ROS). ROS has been shown to promote tissue growth via its effect
on other signalling pathways such as MAPK as well as its effects on satellite cell
proliferation, which ultimately leads to muscle growth (Kawada and Ishii, 2005,
Tanimoto et al., 2008). While ROS is known to increase during ischaemic
conditions, particularly during reperfusion (Korthuis et al., 1985), and has also been
shown to be elevated following HLRE, there is currently no evidence to suggest that
markers of oxidative stress are elevated following acute bouts of BFR-RE (Goldfarb
et al., 2008, Takarada et al., 2000a). In contrast to mTOR signalling and ROS
production, muscle myostatin gene expression acts as a negative regulator of
skeletal muscle hypertrophy (Lee, 2004). A decrease in myostatin expression in
response to HLRE appears to be necessary for producing gains in muscle mass
(Roth et al., 2003). Drummond et al., (2008) reported a decrease in myostatin
mRNA expression following an acute bout of knee extension exercise (20% 1-RM)
with BFR (200 mmHg; continuous), however this was not different to non-BFR
LLRE. Following a similar protocol, Manini et al., (2011) did not detect any change
in myostatin mRNA levels following an acute bout BFR-RE or LLRE. However,
Laurentino et al., (2012a) demonstrated similar reductions in myostatin mRNA
levels following an eight week period of BFR-RT (20% 1-RM) and HLRT (80% 1-
RM).
In summary, even though the mechanisms behind the benefits seen with BFR-RT have
yet to be established, it is unlikely that the gains in muscle mass are caused by one

52
single stimuli, but more likely depend on a number of local and systemic growth factors
that work together to result in a net gain in muscle protein synthesis and cell growth
(see Figure 2.2). The above stimuli do not appear to be different to those achieved with
HLRT. Furthermore, more research is needed in these areas to identify both the
circulatory and cellular effects of BFR-RT and their likely time-course adaptations. In
addition, a greater understanding of whether these mechanisms are similar or not to the
commonly known factors responsible for gains in muscle mass following HLRT should
also be of interest. However, while these mechanisms are important to understand
muscle hypertrophy, it should be noted that it was not the aim of the current thesis to
measure these.

53
Figure 2.2 Schematic of the proposed interplay between potential stimuli that may mediate the
hypertrophic adaptive responses to BFR-RT. Training outcomes are represented by dark shaded
boxes. Potential stimuli are represented by light shaded boxes, whereas stimuli that require
further research are represented by clear boxes. Bold arrows indicated a strong link between
proposed stimuli, while dotted arrows indicate potential links requiring further research. Image
adapted from Scott et al., (2014a).
2.3.3 Muscular endurance
From the information reviewed above (section 2.3.1-2.3.2) it appears that the adaptation
in muscle strength and mass following BFR-RT are well established within the
literature. Given that such light-loads or intensities are used during BFR exercise in
combination with relatively high volumes, it may be expected that localised muscular

54
endurance is also enhanced due to the continuous submaximal muscle actions that are
often prescribed (Pope et al., 2013). However, in comparison to adaptations in muscle
strength and mass, less is known about the acute and chronic effects of BFR-RT on the
endurance capacity of muscle (Fujita et al., 2008a, Kacin and Strazar, 2011, Sumide et
al., 2009, Teramoto and Golding, 2006, Wernbom et al., 2006, Counts et al., 2015).
Wernbom et al., (2006) was the first to investigate the effects of an acute bout of BFR-
RE on dynamic muscular endurance. It was observed that the number of repetitions
performed during knee extension exercise with BFR at 20, 30, and 40% 1-RM were
significantly less when compared with non-BFR LLRE. Similarly, more recent
observations have shown that BFR-RE reduces the capacity of total work that can be
completed (i.e. total number of repetitions) compared with LLRE (Downs et al., 2014,
Wernbom et al., 2006). These data suggest that BFR-RE induces fatigue (of type II
muscle fibres) earlier when compared with non-BFR LLRE, and thus the fatigue that
occurs during BFR-RE may contribute to the stimulus for increased strength and
hypertrophy (Rooney et al., 1994). However, while several studies have shown
reductions in total work capacity during an acute bout of BFR-RE, more chronic studies
have shown increases in total work capacity and overall muscular endurance following
training (Kacin and Strazar, 2011, Sumide et al., 2009). In one example, Kacin et al.,
(2011) measured changes in knee flexion endurance following four weeks of training at
15% MVIC to volitional fatigue. Following training, the BFR group increased
endurance performance by 63% compared to 36% following LLRT. In addition, Sumide
et al., (2009) had participants complete eight weeks of BFR-RT (20% MVIC) with
different restriction pressures at 0, 50, 150, and 250 mmHg (cuff width not reported).
The amount of knee extensor muscle work completed during 50 isokinetic contractions
at 180º/s increased significantly for both the 50 and 150 mmHg groups only. Several

55
other studies have demonstrated that BFR cycling induces greater increases in
endurance performance compared to non-BFR cycle training (Esbjornsson et al., 1993,
Kaijser et al., 1990, Nygren et al., 2000, Sundberg, 1994), and also improvements in
maximal oxygen uptake following BFR walking (Park et al., 2010).
Evidence from these and other BFR-RT studies suggest that increases in endurance
capacity with BFR are due to increases in the number of mitochondria (Esbjornsson et
al., 1993), glycogen stores (Burgomaster et al., 2003, Kaijser et al., 1990, Sundberg,
1994) and oxidative enzymes (Kaijser et al., 1990). With growing interest in the area of
vascular function (and its relevance to muscular endurance), more recent studies have
shown that acute bouts of BFR-RE increase post-exercise blood flow, oxygen delivery,
and capillarization, resulting in an overall improvement in microvascular function
(Patterson and Ferguson, 2010, Hunt et al., 2013). Both aerobic training (Prior et al.,
2003) and HLRE (Gavin et al., 2007) have previously been shown to induce
angiogenesis, which is a central contributor to muscle microvascular function. The main
stimuli for inducing skeletal muscle capillarization (angiogenesis) include intramuscular
hypoxic conditions, changes in vascular wall tension/shear stress, mechanical overload
produced during muscular contractions, as well as increases in the amount of
angiogenic transcript expression factors such as vascular endothelial growth factor
(VEGF), hypoxia-inducible factor 1 alpha (HIF-1α) and nitric oxide synthase (NOS). It
might be expected that these factors are not upregulated during BFR-RE/RT due to the
low mechanical tensions produced (i.e. 20-50% 1-RM loads) in comparison with HLRT
(i.e. ≥ 65% 1-RM). However, results from a study by Larkin et al., (2012) showed that
BFR-RE (120 contractions; 40% 1-RM; 220 mmHg restrictive pressure) increased
muscle haemoglobin concentrations, as well as several post-exercise angiogenic
transcript expression factors, including; VEGF, HIF-1α, and neuronal-NOS.

56
Importantly, these responses were shown to be elevated immediately post-exercise and
up to 24 hours post-exercise, which is similar to observations seen following HLRT
(Gavin et al., 2007) and early BFR-RE research (Gustafsson et al., 1999).
Currently, it would appear that more work is needed in this area in order to determine
the exact mechanisms that are involved with increasing muscular endurance following
BFR-RT. In addition, it is not known if some of these circulatory and cellular effects
mentioned are also involved in inducing increases in muscle strength and mass, or if
these responses are different to typical HLRT. However, while the evidence is limited,
it would seem that if suitable training principles are followed (i.e. training specificity),
BFR-RT will not only elicit increases in strength and hypertrophy, but also muscular
endurance. Therefore, if BFR-RE/RT can promote muscular fitness, this may benefit
healthy young populations as well as the elderly and clinical populations.

57
2.4 Neuromuscular function
Several sites within the central nervous system are responsible for the initial increase in
strength that occurs during the first four weeks of HLRT, which are typically not
associated with proportional increases in muscle hypertrophy (Duchateau and Enoka,
2002, Moritani and DeVries, 1979, Sale, 1988). Neural factors related to strength gains
include increased descending drive from supraspinal centres to muscle (e.g. increases in
motor unit firing frequency and rate coding), decreased co-contraction of antagonist
muscles, increased movement coordination, and increased stretch reflex activity (Sale,
1988, Gordon, 2009, Pearce and Kidgell, 2009). For further discussion on these
proposed mechanisms the reader is directed to reviews by Semmler and Enoka (2000),
Folland and Williams (2007), and Carroll et al., (2011).
It has been well established that the neural adaptations that take place following HLRT
implicate a cortical, spinal, and motor unit level (Griffin and Cafarelli, 2005, Carroll et
al., 2011). Several studies have shown that during both isometric and dynamic
HLRE/RT there is a significant increase in motor unit activation as quantified using
surface and intramuscular electromyography (EMG) (Hakkinen et al., 1987, Kamen and
Knight, 2004, Patten et al., 2001). Similar findings have also been reported during BFR-
RE (Takarada et al., 2000c, Yasuda et al., 2006, Moritani et al., 1992, Yasuda et al.,
2009). An increase in the signal amplitude of surface EMG has, by default, been
interpreted as an increase in neural drive (i.e. changes in motor unit firing frequency
and rate coding), which contributes to the increase in force output (Farina et al., 2004,
Aagaard et al., 2002a). However, surface EMG will be affected by changes in anatomy
(e.g. hypertrophy), as well as variations in electrode placement, and the conductivity at
the skin-electrode interface (Merletti and Parker, 2004). Of greater importance to the
current thesis, while surface EMG provides a global measure of muscle activity, it is not

58
a direct measure of the primary corticomotor structures involved in modulating
voluntary force production. To measure changes in spinal cord excitability and motor
unit activation, several HLRT studies have used the Hoffmans reflex (H-reflex) and
volitional wave (V-wave) (Aagaard et al., 2002b, Del Balso and Cafarelli, 2007,
Fimland et al., 2009, Holtermann et al., 2007). These techniques have not been utilized
to determine whether BFR-RT results in similar adaptations in spinal cord excitability
and motor unit activation. However, given that BFR-RT is thought to result in similar
gains in strength when compared to HLRT, it seems plausible to suggest that these
adaptations may implicate spinal mechanisms. Therefore, future studies should measure
changes in H-reflex and V-wave responses following BFR-RE/RT in order to determine
if similar changes in spinal cord excitability and motor unit activation occur when
compared to HLRT.
More recently, a number of HLRT studies have utilized transcranial magnetic
stimulation (TMS) to assess the adaptations that occur within the human primary motor
cortex (M1) and corticomotor tract (Carroll et al., 2002, Goodwill et al., 2012, Jensen et
al., 2005, Kidgell and Pearce, 2010, Kidgell et al., 2010, Lee et al., 2009). The available
data suggests that the M1 and corticomotor tract are the primary (non-musculature)
structures that drive the increases in force production following training (Sanes and
Donoghue, 2000, Porter and Lemon, 1993). To date, no study has examined the
adaptations that occur within the M1 and corticomotor tract following BFR-RE/RT.
Therefore, TMS should be used to quantify changes in synaptic efficacy (i.e. excitation
and inhibition) within the M1, and any changes in neural transmission within the
corticomotor tract following BFR-RE/RT in order to elucidate if similar mechanisms
are responsible for the changes in strength when compared to HLRT. The following
will first introduce the technique of TMS (sections 2.4.1-2.4.1.2, pages 59-62), and

59
secondly review the potential neural adaptations to an acute bout of HLRE and BFR-RE
(sections 2.4.2-2.4.3) and also the effects of training on neuroplasticity (sections 2.4.4-
2.4.5).
2.4.1 Techniques to measure corticomotor function
First developed in 1985 by Barker and colleagues (Barker et al., 1985), TMS is a non-
invasive, safe and painless method used to stimulate the human M1 (Anand and Hotson,
2002, Kobayashi and Pascual-Leone, 2003, Pearce and Kidgell, 2009, Terao and
Ugawa, 2002). The mechanisms and principles of TMS are well covered in reviews by
Hallett (2000, 2007). However, briefly, TMS is applied over a cortical representation,
whereby a brief, large magnetic current is passed through a coil placed over the scalp.
The coil produces a magnetic field that induces a magnetic current that passes through
the scalp, skull, and meninges to the underlying M1 (Anand and Hotson, 2002, Kidgell
and Pearce, 2011, Pearce and Kidgell, 2009). If the current induced by the
electromagnetic field is of significant duration and intensity, it will depolarise the axons
of interneurons that synapse onto corticomotor neurons. This in turn activates
motoneurons, and therefore, motor units, that drive associated muscle activation via a
muscle twitch or contraction (Anand and Hotson, 2002, Kamen, 2004a, Weber and
Eisen, 2002). This muscle activation response can be recorded using surface EMG and
is quantified as a motor evoked potential (MEP; see Figure 2.3) (Kamen, 2004b). The
focus of the electromagnetic field depends on the shape of the stimulation coil.
Different shaped coils may be used, however TMS is typically applied using a circular
coil or a figure-of-eight coil (Wassermann et al., 2008). The circular coil induces a wide
spread electromagnetic field, while the figure-of-eight coil allows for a more focal
stimulation of the M1, and therefore, permits the selective activation of the target

60
muscle (Kobayashi and Pascual-Leone, 2003, Terao and Ugawa, 2002, Wassermann et
al., 2008, Weber and Eisen, 2002).
2.4.1.1 Motor evoked potentials
A motor evoked potential (MEP) is the resultant TMS-evoked muscle response that
represents corticomotor excitability of the tested individual (Hallett, 2000, Kobayashi
and Pascual-Leone, 2003, Wassermann et al., 2008, Weber and Eisen, 2002). The
lowest TMS intensity required to evoke an MEP is referred to as the motor threshold.
To establish the motor threshold it has been suggested that the stimulus intensity be
increased until MEPs reach at least 200 µV in active muscle (active motor threshold,
AMT) or 50 µV in resting muscle (Kobayashi and Pascual-Leone, 2003, Rossini et al.,
1994, Terao and Ugawa, 2002). An example of an MEP recorded from surface EMG is
shown in Figure 2.3. There are several physiological variables that can be assessed by
examining the properties of the recorded MEP and include;
i. Latency (Figure 2.3: B) is a measure of neurotransmission that is taken from the
moment of stimulation to the onset of an MEP (Kidgell and Pearce, 2011). In
healthy individuals, latency is a reliable and reproducible measure that does not
change with training (Hallett, 2000, Hallett, 2007, Pearce and Kidgell, 2009,
Wassermann et al., 2008).
ii. The MEP amplitude (Figure 2.3: C, is the peak-to-valley amplitude of an MEP,
which is represented by the “spike” waveform on the surface EMG (Hallett,
2000, Hallett, 2007) and is a representation of corticomotor excitability (Pearce
and Kidgell, 2009). MEP amplitude is variable between individuals, can be
influenced by changes in anatomy (e.g. hypertrophy), as well as joint angle,
torque, spinal cord excitability, and background EMG (e.g. variations in

61
electrode placement, and the conductivity at the skin-electrode interface
(Merletti and Parker, 2004)). MEP amplitude is dependent upon the baseline
excitability of the target motoneuron pool (Porter, 1985, Weber and Eisen,
2002). This highlights the importance of controlling for muscle contraction
during stimulation, maintaining a percentage (2-10%) of maximum voluntary
isometric contraction (Curra et al., 2002). By doing this it reduces the variability
of measurement and ensures any differences in MEP amplitude are
representative of neural factors rather than the residual outcome of larger pre-
stimulus EMG (Darling et al., 2006, Kiers et al., 1993, Kamen, 2004b).
iii. Following an MEP there is a period of electrical silence that lasts from 50 ms to
300 ms that interrupts ongoing surface EMG activity. This is known as the silent
period (Figure 2.3: D) and represents inhibition of neural drive to the
motoneuron pool. The silent period duration is usually defined as the time from
the onset of the MEP to the return of surface EMG activity (Kobayashi and
Pascual-Leone, 2003, Rossini et al., 1994, Weber and Eisen, 2002). However,
some investigations have defined the silent period as the time interval from the
end of the MEP to the return of surface EMG activity (Kobayashi and Pascual-
Leone, 2003).
Given that MEPs contain information from all stages along the corticomotor
pathway; it is difficult to ascertain the exact site of adaptation with a standard
single-pulse TMS protocol (Hallett, 2000, Hallett, 2007, Reis et al., 2008).
However, the relatively new method of paired-pulse TMS is becoming more
utilized, and offers a more comprehensive understanding as to the exact mechanism
and sites of adaptations within the M1 and corticomotor tract.

62
Figure 2.3 An overlay of five MEPs (displayed in blue) and subsequent average of five MEPs
(displayed in red) obtained from biceps brachii from a single participant during single- and
paired-pulse TMS. For single-pulse TMS; (A) represents the suprathreshold test stimulus and is
followed by (B) a short latency duration measured from stimulus artifact to MEP onset. (C)
Peak-to-peak MEP amplitude. (D) Silent period duration measured from onset of MEP to return
of background EMG activity (E). For paired-pulse TMS; (A1) represents the subthreshold
conditioning stimulus which is followed by (A) the suprathreshold test stimulus, with a short 3
ms interstimulus interval.
2.4.1.2 Paired-pulse transcranial magnetic stimulation
Paired-pulse TMS protocols have been recently used to investigate a number of cortical
properties that cannot be assessed with single-pulse TMS alone (Abbruzzese et al.,
1999, Goodwill et al., 2012, Reis et al., 2008). This technique requires the application
of two stimuli (Figure 2.3); the first being a subthreshold conditioning stimulus which is
proceeded by a second suprathreshold test stimulus, resulting in descending volleys that
elicit an MEP (Hallett, 2000, Sommer et al., 2001). The interstimulus interval (ISI) is
the time period between the two stimuli, and influences the behaviour of cortical
interneurons (Chen et al., 2008, Hallett, 2000, Hallett, 2007). For example, a short (≤ 5
ms) ISI inhibits (suppresses) and a longer ISI (5-30 ms) facilitates (increases) the MEP
amplitude (Hallett, 2000, Reis et al., 2008, Sommer et al., 2001). Changes in the levels
of inhibition or facilitation observed in the MEP amplitude following an intervention
such as HLRT and BFR-RT may provide a more direct indication of the cortical
mechanisms underpinning the observed increase in muscle strength and function.

63
2.4.2 Acute neural responses to heavy-load resistance exercise
Several lines of evidence suggest that an acute bout of HLRE results in an increase in
both surface and intramuscular EMG of the active limb muscle (Hakkinen et al., 1987,
Kamen and Knight, 2004, Patten et al., 2001), and this response has been associated
with an increase in neural drive and recruitment of larger motor units (Sale, 1987,
Aagaard et al., 2002a). More recently, several studies have used TMS to examine the
acute modulation of corticomotor excitability and inhibition within the M1 and
corticomotor tract following HLRE interventions (Jensen et al., 2005, Selvanayagam et
al., 2011, Sacco et al., 2000, Sacco et al., 1997, Søgaard et al., 2006, Teo et al., 2012,
Carroll et al., 2008, Hortobágyi et al., 2011). In one early study, Jensen et al., (2005)
observed no acute change in corticomotor excitability following five sets of 6-10
repetitions of the elbow flexors (80% 1-RM). However, corticomotor excitability
increased following a motor learning skill task of the same muscle group (Jensen et al.,
2005). This lead to the assumption that different neuromuscular adaptations occur
following motor skill exercise and HLRE (Jensen et al., 2005). However, there is a
compelling argument to suggest that HLRE should be considered a form of skill
training (Pearce and Kidgell, 2009, Leung et al., 2015), as learning seems to be a
prerequisite or important factor in driving changes within the M1 (Carroll et al., 2002,
Jensen et al., 2005, Sale, 1988). During exercise, the nervous system must act by
increasing activation of muscles that contribute to movement in the desired direction
(i.e. agonists or synergists), or by reducing the activation of muscles that oppose
movement in the desired direction (i.e. antagonists). Since several motor learning skill
task studies have shown rapid changes in the organisation of movement representations
in the M1 in the form of expansion and increased excitability of the cortical
representation of specific muscles involved in the tasks (Classen et al., 1998, Jensen et
al., 2005, Pascual-Leone et al., 1995, Perez et al., 2004), it may be plausible to expect

64
that similar changes in excitability and inhibition within the M1 and corticomotor tract
may be responsible for the changes following motor learning skill tasks including
HLRE (Aagaard et al., 2002a, Ziemann et al., 2004).
The data available concerning the acute modulation of corticomotor excitability and
inhibition following an acute bout of HLRE are limited in comparison with the HLRT
and motor learning literature (Jensen et al., 2005, Selvanayagam et al., 2011, Sacco et
al., 2000, Sacco et al., 1997, Søgaard et al., 2006, Teo et al., 2012, Carroll et al., 2008,
Hortobágyi et al., 2011, Duque et al., 2008). Several studies have investigated the
impact of fatiguing contractions on corticomotor excitability and observed an increase
in MEP amplitude during sustained (Sacco et al., 1997, McKay et al., 1996) and
intermittent isometric MVICs (Søgaard et al., 2006, Samii et al., 1996, Benwell et al.,
2006). This is then followed by a brief post-exercise facilitation (Lentz and Nielsen,
2002, Ljubisavljević et al., 1996), and then a period of depressed excitability (Sacco et
al., 2000, Benwell et al., 2006, McKay et al., 1995, Zanette et al., 1995, Brasil-Neto et
al., 1993a). In addition, alterations in inhibition (measured via changes in cortical silent
period duration and short-interval intracortical inhibition [SICI]) have also been
observed to progressively increase during sustained (McKay et al., 1996) and
intermittent isometric MVICs (Benwell et al., 2006), followed by a continued increase
post-exercise (Benwell et al., 2006). While this information is important in the context
of central fatigue during and following muscular contractions, the exercise protocols
used in the aforementioned studies are not typically performed as part of an HLRT
programme, therefore, the following will focus on further TMS studies utilizing more
typical HLRE protocols.

65
When TMS is applied over a cortical representation on the M1, it induces a twitch
response in the target muscle. Recent evidence suggests that repetitive movements in
the opposite direction of the TMS induced twitch can transiently increase M1
excitability and reduce inhibition in the hand, arm, and leg areas (Giacobbe et al., 2011,
Classen et al., 1998, Perez et al., 2004). While this provides evidence of acute changes
in excitability in the M1 following repetitive motor learning practice sessions,
Selvanayagam et al. (2011a) used a similar technique to investigate TMS induced
twitches following various bouts of resistance exercise of the wrist flexors/extensors.
The three resistance exercise sessions were ballistic sustained contraction, fast ballistic
contraction, and slow sustained contraction (i.e. traditional HLRE). For up to 25
minutes post-exercise, the TMS induced twitch force vectors shifted towards the
training direction in all three groups, indicating that the corticospinal connections
involved in force production produced during the intervention were strengthened.
Furthermore, following repetitive exercise tasks of the hand muscles, both Duque et al.,
(2008) and Carroll et al., (2008) observed a significant increase in corticomotor
excitability immediately post-exercise. When examining larger muscles of the upper
arm, corticomotor excitability has also been shown to increase during sustained
isometric contractions (Sacco et al., 1997) and following traditional HLRE of the elbow
flexors (Leung et al., 2015). In contrast, no change in MEP amplitude was reported
following exercise of the hand muscles at 80% MVIC (Hortobágyi et al., 2011), or
following five sets of 6-10 repetitions of the elbow flexors (load not reported) (Jensen et
al., 2005). Given that surface and intramuscular EMG provide evidence of enhanced
motor unit activation during HLRE, and this response is driven by increased excitability
and decreased inhibition within the M1 as assessed using TMS, it would seem from
these data that if BFR-RE involves a component of skill (e.g. completing each repetition

66
to an external timing stimulus) and is more challenging to the central nervous system,
similar adaptations may occur.
2.4.3 Acute neural responses to blood flow restriction resistance exercise
The acute neuromuscular response to BFR-RE has been widely investigated and have
been previously reviewed (Karabulut et al., 2007, Pearson and Hussain, 2014, Pope et
al., 2013), with the majority of studies examining alterations in motor unit recruitment
and their associated muscle fibres using EMG (Takarada et al., 2000c, Yasuda et al.,
2006, Moritani et al., 1992, Yasuda et al., 2009, Wernbom et al., 2009, James and
Karabulut, 2013, Karabulut and Perez, 2013, Yasuda et al., 2008, Yasuda et al., 2010b,
Yasuda et al., 2012a). Under normal exercise conditions, motor units are recruited from
smallest to largest as contractile force increases (Henneman et al., 1965, Rothwell,
1994, Kandel et al., 1991). However, it has been found that during eccentric
contractions (Nardone et al., 1989) and under hypoxic/ischemic conditions the general
order of motor unit recruitment is altered (Takarada et al., 2000c, Yasuda et al., 2006,
Moritani et al., 1992, Yasuda et al., 2009). Several surface EMG studies provide
evidence for greater recruitment of larger motor units during BFR-RE in comparison
with LLRE, despite the light-intensity of contraction (20-50% 1-RM or MVIC)
(Takarada et al., 2000c, Yasuda et al., 2006, Moritani et al., 1992, Yasuda et al., 2009).
An early study by Moritani et al., (1992) examined the inter-relationship between
ischemia/oxygen supply and motor unit activity during intermittent isometric (20%
MVIC) hand grip muscle contractions. Participants performed repeated isometric
contractions (2 second contraction followed by 2 second rest period) for 4 minutes. In
the experimental condition, BFR (200 mmHg) was applied to the upper arm between
the first and second minute via a cuff inflator, and then released for the final 2 minutes
of exercise. Prior to BFR, a consistent pattern of low-amplitude motor unit activity was

67
observed, and there were no differences between the control condition and the BFR
exercise. However, during BFR there was a significant increase in both mean motor unit
spike amplitude and firing frequency (as quantified by surface EMG) compared to
control, and this was also maintained during the recovery period up to 1 minute after the
release of the BFR. In another example, Takarada et al., (2000c) examined the effects of
BFR at different pressures during elbow flexion exercise. Participants were allocated to
either a traditional HLRE protocol (80% 1-RM; x 10 repetitions), or a light-load (~40%
1-RM x 20 repetitions) protocol and BFR was applied in both conditions at pressures of
0 (sham), 50, and 100 mmHg. During exercise without BFR, the relative surface EMG
was approximately 40% lower in the LLRE protocol compared to HLRE. As the BFR
pressure was increased, the relative surface EMG activity during HLRE did not change.
However, during LLRE in combination with BFR the relative surface EMG gradually
increased at 50 mmHg, and at 100 mmHg there were no significant differences between
BFR-RE and HLRE. This finding is in agreement with Yasuda et al., (2008) who found
that as the BFR cuff pressure increased during elbow flexion exercise (20% 1-RM),
muscle activation also increased with the highest pressure utilized (120% systolic blood
pressure; 147 mmHg) being significantly greater than LLRE without BFR. Most studies
report greater increases in muscle activity during BFR-RE compared with non-BFR
LLRE, however, it may be important to note that when the prescribed exercise protocol
is completed until muscular failure there appears to be no difference (Wernbom et al.,
2009, Cook et al., 2014). While these studies examined the surface EMG activity of the
active limb muscle, similar increases in surface EMG activity have also been observed
in the non-restricted trunk musculature (pectoralis major) during bench press exercise
with BFR (Yasuda et al., 2006, Yasuda et al., 2010b).

68
The stimuli behind the greater EMG activity during BFR-RE are currently unknown
(see Figure 2.2, page 53). However, it has been speculated that the increase may be due
to blood pooling, accumulation of fatiguing metabolites (such as lactate and hydrogen
(H+) ions), reduction in muscle oxygen and increased carbon dioxide levels, depletions
in muscle glycogen, or a combination of all of these factors (Karabulut et al., 2007,
Moritani et al., 1992, Yasuda et al., 2010b). In addition, it would seem that several of
these stimuli may activate group III and IV muscle afferent feedback. As an example,
group III and IV afferent feedback respond to reduced tissue oxygenation and the
accumulation of metabolites which may potentially stimulate muscle activation via
altered sensory feedback (Haouzi et al., 1999, Leonard et al., 1994, Moritani et al.,
1992, Rotto and Kaufman, 1988). Overall, this would suggest that to overcome the
rapid fatigue of small motoneurons and their type I muscle fibres, higher threshold
motoneurons and their associated type II muscle fibres are being recruited which may
be one of the mechanisms driving the increase in strength and hypertrophy following
training.
The surface EMG data provides evidence to suggest that BFR-RE increases motor unit
firing and spike amplitude which is normally only associated with HLRE. However,
this evidence only supports an alteration in muscle activation patterns but does not
provide any information about the contribution of the M1 and corticomotor tract that
may modulate voluntary force production. Furthermore, given that corticomotor inputs
are essential for motor unit recruitment, it seems plausible to suggest that during BFR-
RE there may be some form of modulation within the M1 that is responsible for the
recruitment of high threshold motoneurons and their associated fast-twitch muscle
fibres. Evidence for this has been obtained using TMS during ischemic nerve
deafferentation via an external pressure cuff (Ridding and Rothwell, 1995, Brasil-Neto

69
et al., 1993b, Brasil-Neto et al., 1993a, Vallence et al., 2012, Ziemann et al., 1998a,
Ziemann et al., 1998b) or pharmacological blockade (Weiss et al., 2004). Of note, none
of these studies used an exercise intervention, and only examined responses during
and/or following resting ischemic conditions. Ziemann et al., (1998a) applied a
tourniquet across the elbow (distal to the biceps brachii) to a pressure of 200-250
mmHg. This pressure was kept constant until complete ischemic nerve block to the
hand muscle (abductor pollicis brevis) was achieved (31.7 ± 3.8 min). When tested with
single and paired-pulse TMS, ischemia led to a rapid increase in MEP amplitude in
muscles proximal to the ischemic nerve block (biceps brachii), and this effect was
present for at least 60 min after deflation of the tourniquet (Ziemann et al., 1998a). Due
to limitations in testing techniques, some authors have been unable to distinguish
whether the changes in MEP amplitude were due to changes in cortical or spinal
excitability (Ridding and Rothwell, 1997). However, because subcortical and spinal
excitability (using transcranial electrical stimulation, and H-reflexes) did not change
with ischemia, the current evidence suggests that the changes detected with TMS are
due to changes in excitability confined to the M1 (Brasil-Neto et al., 1993b). Therefore,
it appears that the rapid and long lasting (≥ 60 min) increase in MEP amplitude from
muscles immediately proximal to the external compression cuff reflect changes in the
excitability or representation of these muscles at the level of the M1 (Brasil-Neto et al.,
1993b, Ridding and Rothwell, 1995). The increase in MEP amplitude is suggested to be
mediated by the strengthening (e.g. long term potentiation) or weakening (e.g. long
term depression) of pre-existing synaptic connections (Ziemann et al., 1998b), or the
removal of local inhibition of corticomotor neurons that are responsible for movement
in the target muscle proximal to the external pressure cuff (Ziemann et al., 1998a).

70
Currently, there are no studies that have utilized TMS to assess the acute change in
excitability and inhibition within the M1 or corticomotor tract following BFR-RE. From
the available data, it is clear that following an acute bout of HLRE there are rapid
changes in excitability and inhibition, which may be influenced by changes in the
maximal muscle compound action potential (e.g. following fatiguing exercise) when
assessed using TMS. Given that motor unit recruitment is modulated by corticomotor
inputs, it seems reasonable to hypothesise that BFR-RE may also result in similar
changes in excitability and inhibition. Direct evidence from ischemic nerve
deafferentation studies indicate that during ischemia there are rapid and long lasting (≥
60 min) increase in excitability and reduced inhibition are confined to the M1.
Therefore, future studies utilising TMS are needed to measure changes in excitability
and inhibition during BFR-RE to determine whether similar changes occur when
compared to HLRE.
2.4.4 Chronic neural adaptations following heavy-load resistance training
Despite TMS being available since the mid-1980s it was not until the early 21st
century
that TMS was used to investigate corticomotor changes following HLRT (Carroll et al.,
2002). In recent years there has been a growing interest in using TMS to measure
neuromuscular adaptations following HLRT, however, unlike motor skill training,
results have been inconsistent (Pearce et al., 2012, Kidgell et al., 2010, Goodwill et al.,
2012, Weier and Kidgell, 2012, Weier et al., 2012, Carroll et al., 2002, Griffin and
Cafarelli, 2007, Beck et al., 2007, Jensen et al., 2005, Lee et al., 2009, Selvanayagam et
al., 2011, Hortobágyi et al., 2011, Carroll et al., 2009, Hortobágyi et al., 2009, Schubert
et al., 2008, Latella et al., 2012, Leung et al., 2013, Christie and Kamen, 2013, Hendy
and Kidgell, 2013). For example, Carroll et al., (2002) provided the first investigation to
examine the effect of HLRT on corticomotor excitability. Participants completed 12

71
supervised resistance training sessions over a four week period that involved four sets
of six finger abduction-adduction cycles at 70-85% 1-RM. Although maximal strength
increased significantly by 33.4% following training, these authors found no change in
corticomotor excitability and actually observed a reduction in the amplitude of the MEP
following training when elicited by TMS. Similarly, Jensen et al., (2005) had subjects
perform dynamic HLRT of the biceps brachii muscle three times per week for four
weeks. Following training, dynamic muscle strength increased by 31%, however, this
was also accompanied by a decrease in MEP amplitude. In contrast to these findings,
several HLRT studies have reported increases in strength that are generally associated
with the adaptations observed in corticomotor excitability and inhibition. While few
studies have attempted to examine the time-course adaptations in corticomotor
excitability and inhibition (Griffin and Cafarelli, 2007, Latella et al., 2012), for the
purpose of this review the following data will be presented examining the short-term
(i.e. ≤ 4 weeks) followed by longer term training studies (≥ 6 weeks).
Following four weeks of HLRT of the tibialis anterior (six sets of 10 MVICs), maximal
strength increased by 10% at week two and by 18% at week four (Griffin and Cafarelli,
2007). MEP amplitude also increased significantly by 32% after training (Griffin and
Cafarelli, 2007). In a similar study assessing the tibialis anterior, Beck et al., (2007)
reported a 9.5% increase in MEP amplitude following four weeks of ballistic resistance
training. In addition, following three weeks of HLRT (80% 1-RM) of the elbow flexors,
Leung et al., (2013) demonstrated a 39% increase in 1-RM strength which was
accompanied by a ~130% increase in MEP amplitude. Typically, the adaptations in
corticomotor excitability following HLRT are only examined using TMS after short-
term training programmes lasting approximately 2-4 weeks (Kidgell et al., 2010,
Kidgell and Pearce, 2010, Goodwill et al., 2012, Weier and Kidgell, 2012, Hendy and
Kidgell, 2013, Leung et al., 2013, Griffin and Cafarelli, 2007, Carroll et al., 2002,

72
Carroll et al., 2009), or only measure the excitability of spinal motoneurons following
longer-term training (Enoka, 1997, Enoka and Fuglevand, 2001). As the resistance
training programme progresses, further increases in strength are thought to be mainly
influenced by morphological adaptations such as muscle hypertrophy, and therefore
may present some difficulties in determining the long-term adaptations in corticomotor
excitability. Nevertheless, two studies have examined adaptations in M1 excitability
following eight weeks of HLRT and reported mixed findings (Hortobágyi et al., 2011,
Latella et al., 2012). Latella et al., (2012) reported no change in MEP amplitude
following an eight week leg press training program, despite a 29% increase in strength,
while Hortobágyi et al., (2011) observed a 49.9% increase in MVIC of the first dorsal
interosseous and up to 63.9% increase in corticomotor excitability following eight
weeks of training. It is not known why there is such disparity in the literature regarding
adaptations in corticomotor excitability following HLRT, but this perhaps may be
explained by different training methods employed (training design, muscles trained,
frequency, and duration) and the protocols used to assess M1 and corticospinal
excitability being different between studies. Therefore, this potentially limits our
understanding on how the central nervous system adapts to a HLRT programme.
Although these previous TMS resistance training studies have measured corticomotor
excitability, only recently have studies been conducted to measure the effects of training
on intracortical inhibition via examining changes in silent period duration or SICI
(Christie and Kamen, 2013, Weier et al., 2012, Goodwill et al., 2012, Hendy and
Kidgell, 2013, Latella et al., 2012, Hortobágyi et al., 2011). Reduced inhibition has
been suggested to alter the net excitability of the M1, which may be one of the
underlying neurophysiological factors responsible for the increase in motor
performance and strength following an intervention (Kidgell and Pearce, 2010, Perez

73
and Cohen, 2008). In one example, four weeks of isometric MVIC resistance training of
the small hand muscles improved strength significantly (33.8%) in conjunction with a
25 ms reduction in silent period duration (Kidgell and Pearce, 2010). Further evidence
is available from the same authors whereby they examined the time-course adaptations
in strength and silent period duration following eight weeks of unilateral leg press
training at 70-88.5% 1-RM (Latella et al., 2012). Interestingly, while MEP amplitude
remained unchanged, muscle strength increased and silent period duration decreased at
weeks four and eight in both the trained and untrained limb suggesting a cross-transfer
of training effect (Latella et al., 2012). This finding is in agreement with more recent
studies that have observed 21% and 32% reductions in SICI following short-term
lower-body resistance training programs (Goodwill et al., 2012, Weier et al., 2012).
Based on the available datum, while an acute bout of HLRE can lead to transient
changes in excitability and inhibition, it would appear likely that sustained, cumulative
changes may occur that are responsible for the longitudinal neural adaptations that
enhance strength. Given that several studies have shown changes in the functional
properties of the M1 and corticomotor tract following HLRT that has emphasised a skill
element, and considering BFR-RT has been shown to produce similar gains in muscular
strength, it seems reasonable to hypothesise that BFR-RT may result in similar
adaptations.
2.4.5 Chronic neural adaptations following blood flow restriction training
As discussed previously, the early increase in strength associated with short-term HLRT
is largely attributed to adaptations in neural mechanisms given the lack of any muscle
hypertrophy. However, during BFR-RT there are large increases in muscle mass that
may occur within 1-2 weeks of training which are not normally associated with HLRT.

74
However, there is limited available evidence assessing the time-course changes in
muscle strength and hypertrophy following BFR-RT. In a meta-analysis by Loenneke et
al., (2011f) it was observed that strength did not significantly increase until the 10th
week time-point following BFR-RT. The authors speculated that the traditional training
adaptation paradigm (Figure 2.1) may be reversed. However, this result must be viewed
with caution as only 11 studies met the inclusion criteria for the analysis, and only 5 of
these utilized resistance training as the mode of exercise (Abe et al., 2005b, Abe et al.,
2005c, Kacin and Strazar, 2011, Madarame et al., 2008, Fujita et al., 2008b). In
addition, none of these studies used any techniques to measure any changes in the
functional properties of the central nervous system. Furthermore, as presented in the
current thesis, there is a vast quantity of literature that has shown significant increases
in maximal strength from as little as one week of BFR-RT.
There is limited data available that has assessed any chronic change in neuromuscular
function following BFR-RT. In addition to several surface EMG studies that have
reported an increase in neural drive following BFR-RT (Takarada et al., 2000c, Yasuda
et al., 2006, Moritani et al., 1992, Yasuda et al., 2009, Yasuda et al., 2010b), three
studies have utilized the twitch interpolation technique (Moore et al., 2004, Kubo et al.,
2006, Cook et al., 2014) in order to determine changes in maximal motor unit
activation. The twitch interpolation technique consists of superimposing an electrically
evoked single twitch during an MVIC and comparing the response to the resting twitch
response (Millet et al., 2011). In a study by Moore et al., (2004a), following eight weeks
of BFR-RT of the elbow flexors (50% 1-RM), resting twitch torque decreased by 21%,
despite a 22% increase in dynamic strength. In addition, motor unit activation was not
altered following training, potentially due to the already high activation level observed
prior to training (~98%). In agreement with these findings, Kubo et al., (2006) observed

75
no change in activation levels of the knee extensors following 12 weeks of BFR-RT or
HLRT. It should be noted that the interpolated twitch technique (as well as surface and
intramuscular EMG) is only a peripheral measure of the neuromuscular system, and not
a direct measure of the primary supraspinal structures involved in modulating voluntary
force production. Therefore, the limitation of the current BFR data is that it provides no
information regarding changes in cortical function following a training programme.
However, when considering the neuromuscular effects of ischemic nerve
deafferentation, the training-related effect of BFR may lead to use-dependent changes
in corticomotor function in the form of long-term potentiation. Therefore, if similar use
dependent plastic changes are observed following HLRT, then this would provide
support for BFR-RT being suitable not only for populations with reduced functional
capacity of muscle, but perhaps also for populations with neuromuscular impairments
where the benefits of resistance training are even more difficult to achieve.

76
2.5 Haemodynamic function
Previous research investigating the adaptation of the cardiovascular system to exercise
has mainly focused on aerobic training, since aerobic forms of exercise have been
endorsed for use by health organisations such as the American College of Sports
Medicine and the American Heart Association (Haskell et al., 2007, Williams et al.,
2007). More recently, HLRT has received similar endorsement (Kraemer et al., 2002,
Vanhees et al., 2012, Piepoli et al., 2011, Williams et al., 2007), and while HLRT may
be the most effective for developing skeletal muscle strength and hypertrophy, HLRT
induces a high acute cardiovascular stress. For example, while both aerobic and
resistance exercise increase heart rate (HR), stroke volume (SV), and cardiac output (Q̇ )
in order to meet the requirement of the exercise task (Fleck, 1992), it would seem that
the significantly higher elevations in blood pressures (BP) associated with HLRT poses
a high acute stress to the cardiovascular system, particularly for those with any
underlying cardiac or vascular diseases. Therefore, in some instances, HLRT may be
only cautiously prescribed to clinical or elderly populations despite the potential
benefits to reduce muscle atrophy and improve overall functional capacity (Pollock et
al., 1994).
The acute responses and chronic adaptations to the cardiovascular system following
HLRT have previously been reviewed by Fleck (1988, 1992). In comparison, the BFR-
RT literature has mainly focussed on the adaptations to skeletal muscle strength and
hypertrophy, and only recently has the cardiovascular responses been reviewed (Pope et
al., 2013, Loenneke et al., 2011b, Horiuchi and Okita, 2012). Some of these
investigations measured haemodynamic variables during aerobic exercise/training such
as BFR walking and cycling (Abe et al., 2010, Loenneke et al., 2011e, Ozaki et al.,
2011a, Renzi et al., 2010, Sakamaki et al., 2008, Ozaki et al., 2010, Kim et al., 2012a,

77
Sakamaki-Sunaga et al., 2012), while others examined the acute responses to BFR-RE
(Takano et al., 2005, Hollander et al., 2010, Kacin and Strazar, 2011, Fahs et al., 2011b,
Rossow et al., 2012, Vieira et al., 2012, Downs et al., 2014, Rossow et al., 2011, Poton
and Polito, 2014, Araújo et al., 2014), and chronic adaptations following BFR-RT (Fahs
et al., 2011a, Fahs et al., 2011b, Kacin and Strazar, 2011, Kim et al., 2009, Clark et al.,
2010, Patterson and Ferguson, 2010, Evans et al., 2010, Ozaki et al., 2012, Satoh, 2011,
Nakajima et al., 2010). However, while there are numerous studies examining the acute
haemodynamic responses to BFR-RE, these are seldom done in comparison with
traditional HLRE (Neto et al., 2014b, Downs et al., 2014, Poton and Polito, 2014,
Araújo et al., 2014). In addition, the long term (≥ 6 weeks) haemodynamic adaptations
to BFR-RT have been scarcely examined, particularly in comparison with that of
HLRT. Therefore, if BFR-RE/RT is to be recommended as a suitable alternative to
HLRE/RT with moderately equivalent outcomes in muscle functional capacity, then a
greater understanding of the impact BFR has on the cardiovascular system is warranted.
Peripheral vascular adaptations during and following BFR-RE/RT have been reported
previously (Evans et al., 2010, Kim et al., 2009, Horiuchi and Okita, 2012, Hunt et al.,
2013, Downs et al., 2014, Fahs et al., 2011a, Fahs et al., 2011b) and reviewed by
Horiuchi et al., (2012). While these adaptations are important, it is not the purpose of
this thesis to examine these responses. Therefore, the following review of the literature
will examine the haemodynamic properties of the cardiovascular system in response to
BFR-RE and BFR-RT. In addition, key comparisons will be made with the current
HLRE/RT literature in order to better understand the haemodynamic responses in
relation to traditional resistance exercise/training.

78
2.5.1 Acute responses at rest
The restrictive pressure cuffs are typically inflated at rest prior to performing exercise,
so it is important to examine any haemodynamic responses under resting conditions.
With participants lying in a supine position and cuffs applied to both limbs of the lower-
body, HR has been shown to increase (Iida et al., 2007) but there appears to be no
change in BP (Loenneke et al., 2012c, Iida et al., 2007). It is expected that the increase
in HR under resting conditions is due to significant reductions in SV (Iida et al., 2007,
Karabulut et al., 2011b, Nakajima et al., 2008). The decline in SV has been shown to
occur at BFR pressures as low as 50 mmHg (~28% decrease in SV), and up to 200
mmHg (~41% decrease in SV) (Iida et al., 2007). It has been speculated that the
decrease in SV is due to a reduction in venous return (Iida et al., 2007, Renzi et al.,
2010). Interestingly, despite the increase in HR, Q̇ has also been shown to decrease
during BFR under resting conditions in the supine position (Iida et al., 2007, Iida et al.,
2006). The method of applying BFR (without exercise) under resting conditions in the
supine position is suggested to stimulate systemic cardiovascular effects similar to
normal orthostatic stress (i.e. standing under normal gravity). BFR under resting
conditions has been used to simulate a gravity-like stress response during prolonged bed
rest (Nakajima et al., 2008, Kubota et al., 2008b), and studies have even shown that this
method reduces muscle atrophy and strength normally seen during limb immobilisation
(Kubota et al., 2010, Kubota et al., 2008a), lower-limb suspension (Cook et al., 2010,
Cook et al., 2014), and following surgery (e.g. anterior cruciate ligament
reconstruction) (Takarada et al., 2000b). This may be a particularly useful
countermeasure for individuals during prolonged bed rest due to injury or disease, and
has also been suggested to be beneficial for astronauts during space flights to protect
against cardiovascular deconditioning induced by microgravity during short- and long-
duration spaceflights (Iida et al., 2006, Iida et al., 2007, Hackney et al., 2012).

79
2.5.2 Acute responses during exercise
Heart rate, systolic BP, diastolic BP, and mean arterial pressure (MAP) increase
significantly during the performance of traditional HLRE (Fleck, 1988, Fleck, 1992),
particularly if the exercise involves isometric contractions (MacDougall et al., 1985). It
has been demonstrated that the peak exercising HR and BP responses will generally
increase to a greater extent with an increase in absolute load (Haslam et al., 1988,
Lamotte et al., 2005, de Sousa et al., 2014), during prolonged durations of an exercise
set or increased number of repetitions (Lovell et al., 2011, Gotshall et al., 1999,
Gjovaag et al., 2015), and with increased muscle mass involvement (MacDougall et al.,
1985, de Sousa et al., 2014). Because the magnitude of the cardiovascular response
during resistance exercise depends on the muscle mass involved, muscle tension,
absolute intensity (i.e. load lifted) and duration, it may be expected that HLRE produces
higher demand on the cardiovascular system in comparison with BFR-RE. However,
until recently, studies only examined the peak exercising haemodynamic responses
during BFR-RE with exercise at the same intensity without BFR (Takano et al., 2005,
Kacin and Strazar, 2011, Rossow et al., 2011, Vieira et al., 2012). Table 2.1 compares
the effect of HLRE, LLRE, and BFR-RE on mean peak exercising HR and BP
responses taken during an acute bout of exercise.
In a seminal study conducted by Takano et al., (2005), participants performed knee
extension exercise at 20% 1-RM (1 x 30 repetitions, followed by 3 sets to volitional
fatigue) either with BFR (160-180 mmHg) or without. Peak exercising HR, systolic BP,
diastolic BP, and MAP increased significantly for both BFR-RE and LLRE; however
the change was greater during BFR-RE compared with LLRE (Table 2.1). This is
supported by several walking studies that also found peak exercising HR and BP were
higher during walking with BFR in comparison to without BFR (Renzi et al., 2010,

80
Sakamaki et al., 2008, Abe et al., 2010, Loenneke et al., 2011e). In contrast to these
findings, in another resistance exercise study, during a single set of knee extension
exercise to muscular failure (15% MVIC), no differences were found in peak exercising
HR (Table 2.1) between a group exercising with BFR (230 mmHg) or without (Kacin
and Strazar, 2011). In addition, similar peak exercising HR responses were seen during
two sets of bilateral knee extensions to muscular failure at 30% 1-RM with BFR via
elastic knee wraps (125 ± 22 bpm) compared with non-BFR (134 ± 22 bpm) (Loenneke
et al., 2012f). The contrasting observations for HR and BP between these
aforementioned studies are most likely due to the duration of the exercise bout (i.e.
multiple sets versus single set) and intensity of the exercise. Therefore, it appears that
the peak exercising HR and BP responses are generally higher for BFR-RE compared
with LLRE when the exercise is not performed to volitional fatigue. However, more
research is needed to compare similar training protocols before any definitive
conclusions can be established.
More recent investigations have compared the peak exercising HR and BP responses to
BFR-RE with HLRE (Table 2.1), with contrasting results being reported (Neto et al.,
2014b, Hollander et al., 2010, Downs et al., 2014, Okuno et al., 2014, Vieira et al.,
2012, Araújo et al., 2014). Downs et al., (2014) examined the peak exercising HR and
BP responses during supine unilateral leg press and calf raise exercise during HLRE
(80% 1-RM), LLRE (20% 1-RM), and two BFR conditions; high pressure (146 ± 2
mmHg) or low pressure (95 ± 2 mmHg) BFR. As can be seen in Table 2.1, while the
increase in HR was higher for HLRE and LLRE, both systolic BP and diastolic BP were
greater during BFR-RE. This increased elevation in BP was despite the fact that fewer
total repetitions were completed during both BFR conditions compared with HLRE and
LLRE (Downs et al., 2014). In contrast, both Poton et al., (2014) and Neto et al., (2014)

81
found no differences between the peak exercising HR and BP responses between BFR-
RE and HLRE (Table 2.1). Furthermore, Hollander et al., (2010) showed that HR was
significantly higher during elbow flexion (~100 versus ~82 bpm) and ankle plantar
flexion (~87 versus ~77 bpm) exercise in combination with BFR (~100 mmHg; 30% 1-
RM) compared with HLRE (70% 1-RM). Still, while the BP responses from these
studies may be of some concern in regards to increased haemodynamic stress, the peak
exercising BP responses reported in previous HLRE studies appears to be much greater
than reported for BFR-RE (Table 2.1) (Haslam et al., 1988, Lentini et al., 1993,
MacDougall et al., 1985, Miles et al., 1987). Therefore, future research is needed
comparing similar training protocols before any absolute conclusions can be made.
While these increases are reflective of responses during lower-body exercise, it is also
important to examine the responses following selective upper-body resistance exercise,
as this typically constitutes the basis of fitness training for healthy populations and
patients with limited mobility or following injury. While smaller muscle mass is
involved in upper-body resistance exercise, there are significant increases in mean peak
HR, systolic BP and diastolic BP, primarily due to the fact that sympathetic
vasoconstriction of the lower limb musculature is not attenuated by functional
vasodilation in the same muscles, so total peripheral resistance (TPR) is higher. For
example, following a single set of elbow flexion exercise at 80% 1-RM, both systolic
BP and diastolic BP increased significantly from resting values to 193 ± 10 mmHg and
119 ± 8 mmHg, respectively (Haslam et al., 1988). In support of this, at an exercise
intensity of 95% 1-RM, the mean peak systolic BP and diastolic BP response was
230/170 mmHg (MacDougall et al., 1985). Of note, these upper-body HLRE responses
are similar to, and slightly higher than, the responses seen following lower-body BFR-
RE (Table 2.1). The exact mechanisms resulting in these high BP responses are not

82
completely understood, but are possibly related to an increased Q̇ , high intra-abdominal
and intra-thoracic pressures, performance of Valsalva manoeuvres, increased
intramuscular pressures during isometric contractions, and decreases in TPR. Recently,
Vieira et al., (2012) examined BP responses during unilateral elbow flexion exercise at
30% 1-RM either with BFR (120 mmHg) or without BFR in both young (30 ± 3 yrs)
and older (66 ± 7 yrs) men. Peak exercising systolic BP for young (~185 mmHg versus
~160 mmHg) and older (~240 mmHg versus ~230 mmHg) men were greater during the
BFR condition compared with LLRE. A similar response was also seen for peak
exercising diastolic BP for young (~115 mmHg versus ~100 mmHg) and older (~150
mmHg versus ~125 mmHg) men. The authors noted that the exercising responses were
actually obtained within 15 seconds of exercise cessation during the rest intervals
between sets. Therefore, the BP responses seen in this study are possibly lower than
what would be observed during exercise, due to the reduction in muscle pump and
withdrawal of sympathetic activity (Carter et al., 1999). From the evidence provided, it
appears that an acute bout of BFR-RE induces similar increase in BP compared with
LLRE, while both of these methods produce a smaller increase in BP when compared
with HLRE (Table 2.1).

83
Table 2.1 Examples of representative peak-exercising values for heart rate and blood pressures. Data is Mean ± SEM.
* denotes significantly different from resting values; # significantly different to HLRE; † significantly different to LLRE.
AUTHORS HEART RATE
(bpm)
SYSTOLIC BP
(mmHg)
DIASTOLIC BP
(mmHg)
MEAN ARTERIAL BP
(mmHg)
HLRE LLRE BFR HLRE LLRE BFR HLRE LLRE BFR HLRE LLRE BFR
(Rossow et al., 2012) - - 92 ± 5* - - 151 ± 5* - - 102 ± 2* - - 117 ± 4*
(Takano et al., 2005) - 96 ± 7* 109 ±
15*†
- 155 ±
12*
182 ±
18*†
- 99 ± 21* 105 ±
18†*
- 113 ±
27*
127 ±
12*†
(Kacin and Strazar, 2011) - 139 ±
20*
136 ±
23*
- 204 ±
31*
195 ±
24*
- 122 ±
25*
119 ±
19*
- 150 ±
26*
144 ±
20*
(Downs et al., 2014) 113 ± 5* 113 ± 5* 100 ±
4*#†
134 ± 4* 127 ± 4* 156 ±
7*#†
58 ± 3 57 ± 3* 80 ±
4*#†
~83* ~80* ~105*
(Poton and Polito, 2014) ~135* ~105*# ~120* ~190* ~170*# ~190* ~125* ~105*# ~115*# ~147* ~80* ~140*
(Neto et al., 2014b) ~115* ~115* ~120* ~130* ~130* ~125* - - - - - -
(Loenneke et al., 2012f) - 134 ±
21*
129 ±
23*
- - - - - - - - -
(Vieira et al., 2012) - ~138* ~145*† - ~160* ~190*† - ~100* ~116*† - ~120* ~140*†
(MacDougall et al., 1985) ~170* - - ~320* - - ~250* - - ~270* - -
(Lentini et al., 1993) 143 ± 5* - - 270 ±
21*
- - 183 ±
18*
- - 212 ±
19*
- -
(Haslam et al., 1988) 116 ±
6*†
90 ± 4* - 215 ±
7*†
~165* - 124 ± 6* ~85* - ~160* ~110- -
83

84
In regards to the response of Q̇ , typically no comparative change, or only small
increases in Q̇ are observed during HLRE; which is primarily due to an increased HR
response (Miles et al., 1987, Lentini et al., 1993). However, as the load is reduced and
repetitions increase over longer exercise durations, Q̇ may respond more similarly to
that observed with aerobic exercise, although generally to a smaller degree (Bell, 2008,
Baechle and Earle, 2008, Gjovaag et al., 2015). The data available relating to the acute
response of SV and/or Q̇ response to BFR exercise is limited (Takano et al., 2005, Iida
et al., 2007, Renzi et al., 2010, Ozaki et al., 2010, Karabulut et al., 2011b, Nakajima et
al., 2008, Poton and Polito, 2014). From these studies, SV and/or Q̇ responses have
been measured during supine rest (Iida et al., 2007, Karabulut et al., 2011b, Nakajima et
al., 2008), walk exercise (Renzi et al., 2010), cycling (Ozaki et al., 2010), and also
during resistance exercise (Takano et al., 2005, Downs et al., 2014, Poton and Polito,
2014). Interestingly, Q̇ has been shown to decrease during BFR under resting
conditions in the supine position (Iida et al., 2007, Iida et al., 2006), however, due to the
compensatory increase in HR and TPR it appears that Q̇ increases during BFR-RE
(Takano et al., 2005, Downs et al., 2014). For example, Downs et al., (2014) showed
that Q̇ increased significantly during exercise for HLRE, LLRE, as well as high- and
low-pressure BFR. However, the increase in Q̇ was significantly higher for both HLRE
and LLRE (6.7 ± 6 L/min) compared with both of the BFR conditions (~5.4 ± 0.5
L/min). While these data are complicated due to the fact significantly fewer repetitions
were completed under the two BFR conditions, when matched for the same number of
total repetitions it appears that Q̇ increases similarly for BFR-RE (6.2 ± 1.5 L/min) and
LLRE (6.9 ± 1.5 L/min) (Takano et al., 2005). This finding is in agreement with Poton
et al., (2014), where it was further shown that the increase in Q̇ during exercise was
greater for HLRE (~13 L/min) compared with both LLRE and BFR-RE (~11 L/min).

85
The intensity of HLRE is also important in regards to the acute response of SV. HLRE
is generally associated with no change in SV, or even a decrease in this value,
particularly when high intra-abdominal and intra-thoracic pressures develop, which
limits venous return and end-diastolic volume (Iida et al., 2007, Karabulut et al.,
2011b). This information suggests that Q̇ typically increases during exercise, and it
appears that the change in Q̇ may be dependent on the mode of exercise (e.g. aerobic
versus resistance) and level of exertion (e.g. submaximal versus maximal). For BFR-
RE, it is generally accepted that SV decreases under resting conditions (i.e. no exercise)
and during exercise with increasing levels of applied restriction pressure, and that the
reductions in SV are compensated for by an increase in HR in order to maintain Q̇ (Iida
et al., 2007, Karabulut et al., 2011b, Nakajima et al., 2008). Iida et al., (2007) indicated
that the decrease in SV under resting conditions with BFR were as a result of venous
blood pooling in the vascular and extra-cellular compartments of the limbs (measured
using ultrasonography) due to the restrictive cuffs. However, it is likely that blood
pooling diminishes during muscular contractions due to the muscle pump effect. Further
to this, Takano et al., (2005) observed a 12% decrease in SV during BFR-RE compared
with LLRE without BFR, which was speculated to be due to a decrease in venous return
(i.e. decreased cardiac-preload). Results from Downs et al., (2014) also showed a
decrease in SV during high-pressure BFR-RE, which was significantly decreased
compared with low-pressure BFR-RE as well as HLRE and LLRE. The authors
speculated that the blunted rise in SV seen during BFR-RE may not only be caused by a
decrease in venous return, but alternatively through an increase in vascular resistance
(i.e. increased cardiac after-load). Based on this information, the increase in BP
observed during BFR-RE may largely be dependent on increases in Q̇ due to an
elevated HR response, but not SV (Takano et al., 2005).

86
2.5.3 Post-exercise responses
Several studies have examined the post-exercise time-course response in
haemodynamic variables following HLRE (Bell, 2008, Kenney and Seals, 1993,
Pescatello et al., 2004, Hagberg et al., 1984), and mainly focussed on the response in
HR and BP. It is important to measure the post-exercise responses as chronic reductions
in BP (see section 2.5.4, below) may reflect accumulated post-exercise hypotension
from regular acute exercise bouts (Bell, 2008, Kenney and Seals, 1993, Pescatello et al.,
2004). This response has been observed following acute bouts of aerobic exercise
(Pescatello et al., 1991, Hagberg et al., 1987) and also HLRE (Fisher, 2001, Hagberg et
al., 1984). Post-exercise hypotension usually onsets within 60 min following exercise
(Hannum and Kasch, 1981) and has also been reported to persist for ~12 hours
(Pescatello et al., 1991). Recently, Rossow et al., (2011) compared the effects of an
acute bout of HLRE, LLRE, and BFR-RE on post-exercise BP for up to 60 minutes.
While no effect was seen following BFR-RE or LLRE, in the HLRE group at 60
minutes post-exercise, systolic BP and MAP decreased by ~6% and ~5%, respectively.
In a similar study design by the same research group (Fahs et al., 2011b), there was a
significant effect for time for systolic BP at 15 and 45 min post-exercise whereby
systolic BP was higher than resting values, but no differences between groups.
Therefore, with limited information it is hard to draw any conclusions on the post-
exercise hypotensive response for BFR-RE.
With regard to the post-exercise HR response following BFR-RE, several previous
studies have compared the change to both HLRE and LLRE (Neto et al., 2014b, Okuno
et al., 2014, Loenneke et al., 2012f, Fahs et al., 2011b, Araújo et al., 2014). It has been
observed that HR remains elevated at 15 min (Fahs et al., 2011b), 30 min (Okuno et al.,
2014), 45 min (Fahs et al., 2011b) and 60 min post-exercise (Neto et al., 2014b, Araújo

87
et al., 2014) following BFR-RE. While Neto et al., (2014) reported no differences in the
change in the post-exercise HR response from baseline for BFR-RE compared with
HLRE and LLRE, two other studies found that the increase in HR post-exercise was
higher for HLRE compared with both BFR-RE and LLRE (Okuno et al., 2014, Fahs et
al., 2011b). It is expected that the contrasting results of the aforementioned studies are
most likely due to the different methodologies employed for inducing BFR, as well as
different resistance exercise protocols.
2.5.4 Chronic adaptations at rest
Following a period of training, a decrease in resting HR is one beneficial adaptation that
reduces cardiac workload and lowers the risk of cardiovascular illness during exercise
(Gordon, 2009). This adaptation is commonly observed following aerobic type training
(Carter et al., 2003a), and in some instances following HLRT (Fleck, 1992). While
cross-sectional comparisons of highly resistance trained individuals suggest that they
may not have a lower resting HR in comparison with untrained sedentary individuals
(Smith and Raven, 1986, Pearson et al., 1986, Dhamu et al., 2012), longitudinal studies
(6-20 weeks) have observed significant decreases in resting HR of 4 to 13% following
HLRT (Fleck, 1988, Goldberg et al., 1994). The exact mechanism responsible for the
decreased resting HR is not known, but is expected to be due to an increased
parasympathetic and decreased sympathetic cardiac influence on the heart. Although
sufficient evidence exists with regards to the gain in skeletal muscle strength and mass
following BFR-RT programmes, very few have monitored adaptations to resting HR.
Resting HR does not appear to become reduced following three (Kim et al., 2009) and
four (Kacin and Strazar, 2011) weeks of BFR-RT, or following 10 weeks of BFR walk
training (Ozaki et al., 2011a). While these data appear to be conclusive, the data is

88
limited, therefore more short- and long-term BFR-RT in order to determine if it results
in similar adaptations with HLRT.
Reductions in resting BP are also a common benefit following HLRT (Hagberg et al.,
1984, Katz and Wilson, 1992, Kelley and Kelley, 2000, Lovell et al., 2009, Tsutsumi et
al., 1997), and may be particularly important for individuals with cardiovascular
diseases such as hypertension (Carter et al., 2003b). It has been observed that resting
systolic BP and diastolic BP of highly resistance trained individuals is average, or
slightly below average, when compared to untrained sedentary individuals (Fleck, 1988,
Byrne and Wilmore, 2000, Smith and Raven, 1986). From a meta-analysis in which
subjects performed HLRT for four or more weeks, resting systolic BP and diastolic BP
decreased by ~2% and ~4, respectively (Kelley and Kelley, 2000). As discussed
previously, it has been speculated that chronic reductions in BP may reflect
accumulated post-exercise hypotension from regular acute exercise bouts (Bell, 2008,
Kenney and Seals, 1993, Pescatello et al., 2004). While only two studies have
investigated the post-exercise BP response to an acute bout of BFR, several other
authors have examined the effect of BFR-RT on resting BP (Fahs et al., 2011a, Kacin
and Strazar, 2011, Kim et al., 2009, Ozaki et al., 2011a, Satoh, 2011). Recently, Fahs et
al., (2011a) compared the BP responses between HLRT, moderate-load resistance
training, and BFR-RT following six weeks of training. Resting diastolic BP
significantly decreased by 10% when compared to baseline resting values in the BFR-
RT group only. However, the authors speculated that this appeared to be as a result of a
higher resting diastolic BP in the BFR group prior to training (70 ± 2 mmHg) compared
to HLRT and moderate-load resistance training (both 65 ± 2 mmHg). In contrast with
this study, following four weeks of knee extension exercise at 15% MVIC with BFR
(230 mmHg), resting diastolic BP was observed to increase by 9% (Kacin and Strazar,

89
2011). Regarding clinical populations, patients in Japan with metabolic syndrome (n =
51) completed Kaatsu exercise and improvements in cardiac function were shown over
3-4 months of training (Satoh, 2011). Specifically, 12 out of 18 patients (67%) with
hypertension (defined as systolic BP 150-170 mmHg and/or diastolic BP 90-100
mmHg) reduced their resting systolic BP from an average of 166 mmHg to 146 mmHg,
and diastolic BP from an average of 96 mmHg to 86 mmHg. Overall, this was an
average decrease in resting BP of ~10%. While these improvements in BP in a clinical
population are the first to be reported, it should be acknowledged that this was an
observational study from the authors exercise therapy clinic, rather than a strict
randomized control trial. Other investigations have not reported any change in resting
HR or BP following BFR-RT (Kim et al., 2009, Ozaki et al., 2012, Fahs et al., 2011a)
or walk training (Ozaki et al., 2011a) in healthy populations. From the data available it
is difficult to determine what effect BFR has on resting BP. Therefore, if the objective
of prescribing a resistance training program is to lower resting BP, current evidence
suggests that HLRT may be more useful than BFR-RT. However, more research is
required to establish the efficacy of BFR on resting BP. Therefore, future studies should
attempt to determine what effect an acute bout of BFR has on post-exercise BP
responses. Secondly, longer duration (≥ 6 weeks) training studies should be conducted
in order to assess the time-course of adaptations to BP.
In regards to both resting Q̇ and SV, it appears that there is little evidence to suggest
that any differences in cross-sectional comparisons exist between highly resistance
trained individuals and untrained sedentary individuals (Brown et al., 1983, Dickhuth et
al., 1979). In addition, longitudinal studies generally report no changes in resting Q̇ and
SV following HLRT (Lusiani et al., 1986, Pluim et al., 2000, Shabkhiz et al., 2013). To
date, it is unknown if any adaptations in resting Q̇ and SV occur following BFR-RT.

90
2.5.5 Chronic adaptations during exercise
It would appear that after a period of prolonged training, haemodynamic adaptations
occur not only at rest but also during the performance of exercise, which could be
considered as a reduction in overall cardiovascular stress and/or an improvement in
cardiovascular fitness. Longitudinal studies (12-16 weeks) have shown that HLRT
elicits reductions in peak-exercising HR, BP, and rate pressure product (RPP) when
working at the same absolute intensity in both young (Sale et al., 1994, Goldberg et al.,
1994, Sale et al., 1993) and older participants (McCartney et al., 1993). Furthermore,
cross-sectional comparisons have shown that highly resistance trained individuals
demonstrate lower absolute peak-exercising HR and BP in comparison with untrained
sedentary individuals (Fleck and Dean, 1987).
While there have been some short-term BFR-RT studies that have examined
cardiovascular adaptations to exercise, most of these have observed vascular
adaptations (Evans et al., 2010, Kim et al., 2009, Horiuchi and Okita, 2012, Hunt et al.,
2013, Downs et al., 2014, Fahs et al., 2011a, Fahs et al., 2011b). Therefore, much less is
known about the HR, BP, Q̇ and SV adaptations that occur following short- and long-
term BFR-RT. To the authors’ knowledge, only one study has examined the peak-
exercising responses during BFR-RE before and after a training intervention. Kacin et
al., (2011) had subjects perform knee extension exercise (15% MVIC) to volitional
fatigue, with one leg performing the exercise with BFR (230 mmHg) and the other
without. The endurance test was completed once at baseline, and then again after four
weeks of training. During the baseline test, there were no differences in number of
repetitions completed, or peak-exercising HR and BP, suggesting that both protocols
elicit similar haemodynamic responses when performed to fatigue. Following training,

91
both groups increased the number of repetitions in the endurance test; however the
change was significantly greater for BFR versus control (63% and 36% increase,
respectively). Despite this, the peak-exercising HR and BP did not change relative to
the baseline measurement in the post-test for the BFR group, while HR and diastolic BP
were 11% and 7% higher during the control test. These data suggest that there were no
central cardiovascular adaptations for the BFR group, and that the increase in endurance
performance was due to peripheral factors such as an increase in number of
mitochondria (Esbjornsson et al., 1993), glycogen storage (Burgomaster et al., 2003,
Kaijser et al., 1990, Sundberg, 1994), oxidative enzymes (Kaijser et al., 1990), and
enhanced microvascular filtration capacity and blood flow in the muscle after ischemic
training (Patterson and Ferguson, 2010, Evans et al., 2010). The reader is directed to
section 2.3.3, page 53 for more information about muscular endurance adaptations to
BFR-RT). Of note though, this study had the same participants complete BFR-RT with
one limb, while the other limb trained completed LLRT. With this study design, it
would be difficult to differentiate any differences in cardiovascular adaptations.
Additionally, the results from this study may be limited in that the work completed was
not matched from pre- to post-training. Given that the number of repetitions increased
post-training, a comparison between the two tests regarding peak-exercising responses
cannot be made.
Other studies have shown increases in peak VO2max following 10 weeks of BFR walk
training in older adults (Ozaki et al., 2011b), and also following BFR-RT in patients
with ischemic heart disease (Nakajima et al., 2010). Interestingly, an increase in VO2max
(11.6%) and VEmax (10.6%) was also observed following twice daily BFR walk training
for two weeks in an athletic population (Park et al., 2010). These authors also measured
the acute change in haemodynamic responses during the first and last training session,

92
and found that for the same given intensity, HR was reduced while SV increased, while
subsequently no change was found for Q̇ . While the evidence is limited, it appears that
BFR (aerobic or resistance training) may induce some central and peripheral
cardiovascular adaptations. Therefore, future studies should examine these adaptations
across short- and long-term BFR-RT programs in comparison with traditional methods
such as HLRT and LLRT.
2.5.6 Summary of findings regarding haemodynamic function
It is important to characterise the haemodynamic responses to an acute bout of BFR-RE
in comparison with the responses seen during HLRE and LLRE. While the use of light-
loads may provide a safe alternative to increase muscle function and overall health, if
the applied external pressure stress the cardiovascular system to a higher degree during
BFR-RE/RT compared with HLRE/RT, this mode of exercise may not be considered a
practical alternative to traditional HLRT. Because the data is limited, and many
differences exist in testing and training methodologies, such as the mode of exercise
(e.g. lower- or upper-body), duration of the exercise bout (e.g. single set versus multiple
sets), velocity of the movement, absolute loads used, and whether repetitions were
carried out to volitional fatigue or not, it is difficult to make definitive conclusions (see
Table 2.2). In addition, most of the studies reviewed above were performed in healthy
young populations, and it is possible that BFR-RE/RT may have interactive risks in “at
risk” populations such as the elderly, or those with pre-existing cardiac or vascular
diseases. Therefore, future studies should directly measure the peak-exercising
haemodynamic responses to an acute bout of BFR-RE in comparison with HLRE and
LLRE. Secondly, time-course adaptations in haemodynamic function should be
measured over periods longer than six weeks to assess its effect on acute responses to a

93
single session over time and also the chronic training adaptations following an
intervention. Based on the current findings, while the use of light-loads in combination
with BFR to produce gains in muscle strength and mass appears largely beneficial, it is
recommended that caution should be practiced (e.g. reducing cuff pressure and
duration) for individuals with cardiac or peripheral vascular diseases.
Table 2.2 Summary of acute responses and chronic cardiac and haemodynamic adaptations to
BFR-RE/RT
Acute responses Chronic adaptations
At rest During
exercise
Post-
exercise*
At rest* During
exercise*
HR ↑ ↑↑ ↔ or ↑ ↔ or ? ↔ or ?
Systolic BP ↔ ↑↑ ↔ or ? ↔ or ⇅ ↔ or ?
Diastolic BP ↔ ↑↑ ↔ or ? ↔ or ⇅ ↔ or ?
Q̇ ↓ ↑↑ ? ↔ or ? ?
SV ↓↓ ↑↓ ? ↔ or ? ?
*, minimal data; ↔, no change; ↑↑, majority of studies observe an increase; ↓↓ majority of
studies observe a decrease; ↑ some studies observe an increase; ↓ some studies observe a
decrease; ?, unknown.

94
2.6 Conclusion
The current literature investigating BFR-RE/RT (and other modes of exercise) indicates
promising prospects as an alternative to HLRT to enhance muscular strength, mass,
endurance, and clinical rehabilitation outcomes in populations with limited resistance
training capacities. While HLRT may still provide the greatest stimulus to produce
strength and mass, when matched for the same intensity and volume of training, BFR-
RT appears to be a superior training method compared with LLRT. The efficacy of
BFR-RT on strength is well established, however, the underlying neural mechanisms
responsible for the gain in strength following BFR-RT remain to be elucidated.
Evidence from acute HLRE and ischemic nerve deafferentation studies indicate that
there are rapid and long lasting (≥ 60 min) increases in corticomotor excitability, as well
as decreases in SICI. Similar responses are seen following HLRT, and changes in
corticomotor excitability appear to correspond with motor function and performance,
including muscular force. This indicates a promising outlook for the application of BFR
during resistance training. Furthermore, given that the current knowledge regarding the
effects of BFR during exercise on haemodynamic function is limited and inconclusive,
future research is needed to examine the acute responses to BFR-RE of the upper- and
lower-body, and also the training related adaptations, in order to establish the safety and
efficacy of BFR-RT in comparison with both HLRT and LLRT.
Therefore, the limitation of the current BFR-RE/RT data is that it provides no
information regarding mechanisms underlying the increase in strength (i.e. corticomotor
function). In addition, if BFR-RT is to be recommended as a suitable low risk
alternative to HLRT yet with moderately equivalent outcomes, then a greater
understanding of the impact of BFR on haemodynamic function and perceptual
responses is warranted. The aim of this thesis was to determine the efficacy of BFR-
RE/RT, with particular emphasis on understanding the acute neural, haemodynamic,

95
and perceptual responses to an acute bout of BFR-RE, and how these adapt to
progressive training and de-training in healthy young populations.

96
CHAPTER THREE:
Materials and methods

97
This thesis presents data from three separate studies. The first two studies investigated
unilateral exercise of the elbow flexors (biceps brachii) and assessed the acute effects of
BFR-RE. The final study measured both the acute and chronic adaptations to an eight
week full-body BFR-RT and four week de-training program. All studies compared
BFR-RE/RT to more traditional HLRE/RT and LLRE/RT.
The methods within this chapter will provide general information on the equipment and
techniques used, and any variations to these procedures are noted within the specific
study chapters.
3.1 Participant recruitment and ethics
A total of 61 healthy subjects (19-30 years of age, males n = 49 and females n = 12)
volunteered to take part in the experiments within this thesis. Participants were provided
with verbal and written information on the tasks required to be completed before
participating in the studies. Following this, participants were screened for any medical
contraindications to participation. All participants had no known history of peripheral or
neurological impairment, cardiovascular, pulmonary, or metabolic disease,
musculoskeletal injuries, or self-reported smoking. All participants were physically
active but had no involvement in any kind of resistance training for the previous 6
months prior to participating.
The studies were approved by the Human Research Ethics Committee of Deakin
University (project identification: HREC 2011-228), and written and informed consent
was obtained from each participant prior to taking part in any experiments. All
experiments were conducted according to the standards established by the Declaration
of Helsinki.

98
3.2 Anthropometric measurements
Height and body mass were measured to the nearest 0.5 cm and 0.1 kg, respectively,
using a stadiometer (220 portable stadiometer, Seca, Hamburg, Germany) and digital
electronic scale (UC-321, A&D Co Ltd, USA). Body mass index was then calculated
using the following:
Equation 1:
BMI (kg.m2
) = Body mass (kg)/Height2
(m2
).
3.3 Blood flow restriction protocol
As discussed within the literature review, there are some important variables that need
to be considered when performing BFR, including; cuff width, final restriction pressure,
and restriction durations (i.e. continuous or intermittent). Throughout this thesis the
determination of the final restriction pressure and duration of inflation were different
between studies and will therefore be discussed within the specific study chapters. The
information provided below refers to the general methods employed for BFR only.

99
Figure 3.1 The Zimmer Automatic Tourniquet System (A.T.S) 3000. The device is a dual-port,
dual-cuff medical tourniquet system with microprocessor controls and dedicated ports for
supplying and measuring pressure for each cuff independently. The Zimmer A.T.S 3000 has
Limb Occlusion Pressure (LOP) technology that senses, calculates and reports the cuff pressure
necessary to achieve complete blood occlusion in the limb.
All participants that completed BFR-RE throughout the thesis were familiarised with
the technique prior to beginning their chosen study. The same automatic tourniquet
system (A.T.S. 3000, Zimmer Inc., OH, USA; Figure 3.1) and appropriately sized
pneumatic cuffs were used in all experiments in this thesis. For the upper-body, a
pneumatic cuff (52 cm long, 10.5 cm wide; bladder length 45 cm, bladder width 8 cm;
Figure 3.2, right) was worn around the most proximal portion of the arm and inflated.
For the lower-body, slightly larger cuffs were worn around the most proximal portion of
the thigh (86 cm long, 10.5 cm wide, bladder length 80 cm, bladder width 8 cm; Figure
3.2, left). Similar tourniquet devices (e.g. Kaatsu Master, Hokanson Rapid Cuff
inflator) that maintain a set restriction pressure have been used previously, as well as

100
the wide cuffs for both the lower- and upper-body (Rossow et al., 2012, Wernbom et
al., 2006, Hollander et al., 2010).
Two different methods were used to determine the final cuff inflation pressure
throughout the thesis, and will be discussed within the specific study chapters.
Following the determination of the final exercise pressure, and prior to beginning
exercise, with the participant standing the cuff pressure was repeatedly set (30 s) and
then released (10 s) from an initial pressure of 50 mmHg. The cuff pressure was then
increased by 20 mmHg until the final exercise cuff pressure was reached. This method
was completed to increase participant comfort, has been described previously and used
extensively in research settings (Abe et al., 2006, Fahs et al., 2011b).
Figure 3.2 Placement of restrictive cuffs on the lower-body (left) and upper-body (right).

101
3.4 Muscle strength and mass measurements
3.4.1 Maximum strength
To establish the exercising load used during each trial, each participant completed a one
repetition maximum (1-RM) test following a previously verified protocol (Munn et al.,
2005), with the method similar to that as described by the American College of Sports
Medicine (ACSM, 2013) and the National Strength and Conditioning Association
(Baechle and Earle, 2008). The initial starting weight was chosen based on the
participants’ estimation of strength. Participants were then asked to complete the 1-RM
through a full range of motion. Single repetition lifts were conducted with progressively
heavier loads until failure, which was defined as the final load that could be
successfully lifted with correct technique where an additional 0.5-5.0 kg could not be
successfully lifted. Rest intervals between 1-RM attempts were dependent on
participant readiness but ranged from 2-5 minutes, while not more than 4 repetitions
were completed during any test. If further repetitions were required, participants
attended a subsequent testing session 3-7 days later to continue the assessment (ACSM,
2013, Baechle and Earle, 2008).
3.4.2 Muscle mass
3.4.2.1 Dual energy X-ray absorptiometry
Dual energy X-ray absorptiometry (DXA; Lunar Prodigy, GE Lunar Corp., Madison,
WI, USA) using software version 12.30.008 was used to assess total bone-free lean
body mass (LM), total bone-free fat mass (FM), as well as arm-LM, leg-LM, and trunk-
LM using a total body scan (Figure 3.3, left). DXA has been long considered as
acceptable method for the measurement of body composition, and found to be a valid

102
and reliable measure in young, healthy, active populations similar to those recruited for
studies within this thesis (Moon et al., 2009, Silva et al., 2006, Kerr et al., 2015,
Lohman et al., 2009).
Calibration of the DXA was performed on each testing day prior to scanning
participants, and scanning procedures were standardized for all participants and done in
accordance with recently published best practice protocols for the assessment of whole
body composition (Nana et al., 2015). In addition, all analysis of DXA was undertaken
by a single investigator for consistency. The short-term coefficient of variation
measured on two consecutive days for repeated measurements of total body lean mass
and fat mass in our laboratory ranges from 1.0% to 1.7%. Participants were placed in a
supine position with arms placed close to the sides of the body in a neutral position
within the 60 cm scanning area on the DXA table. Velcro straps were placed around the
ankles to hold the legs together during the scans and prevent any movement.
3.4.2.2 Ultrasound
B-mode ultrasonographic evaluation of skeletal muscle thickness (MTH) was taken at
seven sites from the anterior and posterior aspects of the body using a Sonosite
ultrasound (Springfield, NJ, USA; Figure 3.3, right). All measurements were taken on
the participants’ dominant side with subjects lying in supine and prone positions.
Ultrasound measurements of MTH have been found to be reliable with participants in
either standing or laying positions (Thoirs and English, 2009). A 5-15 Hz scanning
transducer head was lubricated with transmission gel and placed lightly on the marked
area without depressing the dermal surface. Distortion of tissue due to excess
compression was eliminated by observing that no movement of the tissue occurred in
the real-time ultrasound image. When a clear image was visible on the monitor, the

103
Figure 3.3 Example of participant and equipment set up for Dual X-ray Absorptiometry scan
(left of image), and ultrasound device (right of image).
image was captured for immediate analysis. MTH was determined as the distance
between the adipose-muscle interface and muscle-bone interface from the ultrasound
image (Figures 3.4 and 3.5) as per previous protocols (Abe et al., 1994, Yasuda et al.,
2010b). The reliability and validity of ultrasound measurements for determining MTH
has been reported previously to be very high in comparison with magnetic resonance
imaging (Reeves et al., 2004). In addition, reliability trials were conducted for
measurement of MTH by ultrasonography. Specifically, six participants were assessed
on two consecutive days prior to the commencement of the intervention. An average of
five recordings was obtained from each participant and subsequently used for reliability
analysis. No significant difference was detected between the two trials, and the short-
term coefficient of variation for repeated measurements on seven muscle sites (as listed
below) ranged from 1.3% to 6.4%.

104
The anthropometric locations of the seven sites were initially identified with methods
done in accordance with Abe et al., (1994) and Yasuda et al., (2010b). A surgical
marking pen was used to draw a transverse line around the limb at the established level.
Briefly, the seven anatomical landmarks of the sites were as follows (see also Figures
3.4 and 3.5);
Biceps and triceps: on the anterior and posterior surface equal to 60% distal between
the lateral epicondyle of the humerus and the acromial process of the scapula.
Pectoralis major: at the clavicular midpoint and between the third and fourth costa.
Quadriceps and hamstring: on the anterior and posterior surface midway between the
lateral condyle of the femur and the greater trochanter.
Gastrocnemius and tibialis anterior: on the anterior and posterior surface equal to 30%
distal of the lateral condyle of the tibia and the lateral malleolus of the fibula.
To ensure accuracy of the data across all testing time points, the marking sites were
recorded and matched on each testing session.

105
Figure 3.4 Ultrasound images representing muscle thickness for the lower-body. Sample MTH
images taken from A) Quadriceps; B) Hamstrings; C) Gastrocnemius; and D) Tibialis Anterior.

106
Figure 3.5 Ultrasound images representing muscle thickness for the upper-body. Sample MTH
images taken from A) Biceps brachii; B) Triceps brachii; and C) Pectoralis Major.

107
3.5 Neuromuscular measurements
All TMS measurements were taken in accordance with application guidelines for use in
research and clinical settings (Rossi et al., 2009), as well as in accordance with a
checklist from an international expert panel (Chipchase et al., 2012). That is, the
checklist was used to ensure that participant information, methodology, and analytical
information were considered for the study design and are reported in the current
chapter, as well as in each specific study chapters if TMS was used. In addition, the
consensus findings reported typically agree with the current research evidence and are
referenced where appropriate.
3.5.1 Surface electromyography
Surface electromyography (EMG) activity was recorded from the target muscle using
bipolar Ag-AgCI electrodes. Two electrodes were placed over the muscle belly of the
muscle of interest, and one ground reference electrode was positioned on a bone
landmark close in proximity to the muscle of interest. All cables were fastened with
tape to prevent movement artefact. The participants’ skin was shaved and swabbed with
70% isopropyl alcohol prior to electrode placement to ensure a clear signal was
obtained. All surface EMG signals (including MEPs) were amplified (x1000) with
bandpass filtering between 10 Hz and 1 kHz, sampled at 2 kHz and collected on a PC
running commercially available software via a laboratory analogue-digital interface
(PowerLab 8/35 ADinstrument, Australia) for later offline analysis.

108
3.5.2 Transcranial magnetic stimulation
Single- and paired-pulse TMS of the M1 was applied using two Magstim 2002
stimulators (Magstim Co, UK) to produce active MEPs in the muscle of interest. To
ensure consistency of coil placement throughout testing, participants wore a snugly
fitting cap, positioned with reference to the nasion-inion and interaural lines. The cap
was marked with 1 cm spaced sites in a latitude-longitude matrix to ensure consistent
coil position throughout the testing protocol and for repeated testing sessions over the
period of the study. The cap and coil position was checked regularly to ensure the
positioning of the TMS coil was consistent. Sites near the estimated motor area of the
muscle of interest were explored to determine the site at which the largest MEP
amplitude was evoked during a low level contraction (generally defined as no greater
than 2-10% of MVIC). This site was defined as the “optimal” site (the location on the
M1 that evokes the maximum MEP amplitude to the muscle of interest).
3.5.3 Active motor threshold
Active motor threshold (AMT) of the muscle of interest was established as the stimulus
intensity at which an MEP could be obtained with at least 3 out of 5 stimuli with a peak-
to-valley amplitude greater than 200 µV during a low level contraction (Kobayashi and
Pascual-Leone, 2003, Rossini et al., 1994, Terao and Ugawa, 2002).

109
3.5.4 Motor evoked potentials and short-interval intracortical inhibition
Once AMT was obtained, the single-pulse TMS protocol to measure MEP amplitude
comprised 10 unconditioned stimuli. This was followed by 10 paired-pulse stimuli to
induce SICI. The paired-pulse stimuli comprised an initial subthreshold conditioning
stimulus, followed by a suprathreshold test stimulus. The stimulus intensity for TMS
used to elicit MEP amplitude and SICI are identified in each specific study chapter.
For all trials, the intensities used for single- and paired pulse TMS were determined at
baseline (i.e. prior to the exercise intervention). If required, the stimulus intensity was
adjusted at each time-point following each intervention, if there was a change in AMT.
Each stimulus was delivered in random intervals every five to 12 sec to avoid stimulus
anticipation, and 60 sec rest was provided between the single- and paired-pulse stimuli
to reduce the possibility of muscle fatigue.
3.5.5 Maximal compound muscle action potential
Direct muscle responses (MMAX) were obtained for the muscle of interest under resting
conditions at all time-points. A Digitimer (DS7A, Hertfordshire, UK) constant-current
electrical stimulator (pulse duration 1 ms) was used to deliver each electrical pulse via
bipolar electrodes. To ensure maximal responses, the current was increased an
additional 20% and the average MMAX was obtained from 5 stimuli, with a period of 5-
10 seconds separating each stimulus. MMAX were analysed using LabChart software (8,
ADInstruments, Bella Vista, Australia) after each stimulus was automatically flagged
with a cursor, providing peak-to-valley values in μV.

110
3.6 Haemodynamic measurements
3.6.1 Cardiac parameters
In order to measure cardiac output (Q̇ ), an online metabolic system (Innocor, Innovision
A/S, Odense, Denmark) with inert gas re-breathing capability was used as previously
described (Jakovljevic et al., 2008, Fontana et al., 2010). All participants were
instructed on the correct technique required to undertake a re-breathing test in order to
measure Q̇ during each trial where appropriate. This included providing instruction
about the breathing rate, depth and timing required to successfully conduct the test.
Participants would then receive a demonstration re-breathing test from the
author/primary investigator, before a practice test was undertaken by the participant in
‘demonstration mode’ on the Innocor metabolic system. Practice re-breathing tests
would be conducted several times until the author was satisfied that the participant
could successfully perform the technique. During each measurement of Q̇ , participants’
performed a controlled re-breathing manoeuvre using a mixture of inert gases for
approximately five breathing cycles (~4 seconds/cycle). To minimise any effect of
changing abdominal pressures throughout the exercise repetitions (i.e. Valsalva
manoeuvre) on both Q̇ and blood pressure (BP), participants were instructed to inspire
throughout the eccentric phase and expire throughout the concentric phase to enable
maintenance of a constant breathing rate (15 breaths.min-1
) as monitored by a
metronome.
To obtain accurate measures of Q̇ , the Innocor system required input of blood
haemoglobin concentrations and measures of ambient temperature and humidity.
Ambient temperature and humidity were recorded prior to each testing session via a
Hygrometer (Model 608-H1, Lenzkirch, Germany). Prior to commencement of all

111
exercise trials, blood haemoglobin concentration was measured by collecting two
samples of blood into micro-cuvettes (Hemo-Control model 3000-3012-0765, EKF-
Diagnostic, Germany). Blood samples were drawn via a finger-prick using a lancet
(Accu-Chek, Roche-Diagnostics, Manheim, Germany) and analysed through use of an
electronic hemocube (Hemo-control model 3000-0031-680, EKF-Diagnostic,
Germany). If the difference in result was within 0.5 g/dL then an average result was
calculated, if not a third measurement was taken and an average would be calculated.
To measure heart rate (HR), participants were provided with a FS1 Polar electro HR
monitor (Polar Electro, Kempele, Finland), which consisted of a chest strap and wrist
unit. A small amount of ultrasound transmission gel was placed on the transmitter
electrodes to allow for more stable readings. Using measurements of Q̇ and HR during
trials, stroke volume (SV) was subsequently derived using the following:
Equation 2:
SV (ml.min-1
) = (Q̇ (L.min-1
) x 1000) / HR (bpm-1
).
3.6.2 Blood pressure parameters
Blood pressures (systolic BP and diastolic BP) were measured on a non-exercised arm
via manual auscultation using a hand held sphygmomanometer (8 cm cuff width, 54 cm
cuff length) and stethoscope. During all resting measurements (i.e. pre- and post-
exercise), the average BP was recorded from two measurements separated by 1-2 min.
If these were ≥ 5 mmHg apart for systolic BP another measure was included in the
recorded average (Pickering et al., 2005). Multiple measurements of BP were not taken
during exercise due to the time constraints of each exercise protocol. The same
experienced researcher performed all BP measurements.

112
Average coefficients of variation for test re-test reliability of BP taken at baseline for
each participant’s first and second trial was 5.3%. Mean arterial blood pressure (MAP)
was estimated according the methods of Moran et al. (1995):
Equation 3:
MAP (mmHg) = Diastolic BP (mmHg) + 0.01 x exp(4.14 – 40.74) / Heart rate (bpm-1
))
(Systolic BP (mmHg) – Diastolic BP (mmHg))
Total peripheral resistance (TPR) and rate-pressure product (RPP) were also
subsequently derived (Nelson et al., 1974):
Equation 4:
TPR = MAP (mmHg) / Q̇ (L.min-1
)
Equation 5:
RPP = HR (bpm-1
) x Systolic BP (mmHg)

113
3.7 Perceptual measurements
3.7.1 Rating of perceived exertion and pain
Participants were required to provide a self-rating of perceived exertion (RPE; Figure
3.6, left) on a scale of six (no exertion at all) to 20 (maximal exertion) (Borg, 1982). In
addition, ratings of acute pain using a CR-10 scale (Borg, 1998) were also completed,
where a 10 on the Borg CR-10 pain scale (which ranges from 0 = Nothing at all (no
soreness/other pain) to 11 = Absolute maximum (highest possible intensity
soreness/other pain; Figure 3.6, right) (Borg, 1998). Participants were exposed to the
RPE and CR-10 scales during each study familiarisation.
Figure 3.6 Example scale of Borgs’ ratings of perceived exertion (left) and pain (right).

114
3.7.2 Delayed onset muscle soreness
Delayed onset muscle soreness (DOMS) was evaluated using a visual analogue scale
(VAS) of a 100 mm continuous line that represents “no pain” at one side (0 mm) and
“unbearable pain” at the other side (100 mm; Figure 3.7). Participants were asked to
report the soreness level on the line after palpating the muscle of interest and moving
through a full range of motion. Participants were asked to quantify the level of muscle
soreness on the first day following the intervention, and then for a maximum of five
days or until no pain were reported, as per previous protocols (Chen and Nosaka, 2006,
Lavender and Nosaka, 2008).
Figure 3.7 Example of the visual analogue scale used to measure delayed onset muscle
soreness.

115
CHAPTER FOUR:
Neuromuscular responses to an acute bout of
blood flow restriction resistance exercise
Adapted from:
Brandner CR, Warmington SA, Kidgell DJ.
Corticomotor excitability is increased following an acute bout of blood flow restriction
resistance exercise. Frontiers in Human Neuroscience, 2015; 9:652.
doi: 10.3389/fnhum.2015.00652

116
4.1 Introduction
Blood flow restriction (BFR) in combination with light-load resistance exercise (BFR-
RE; 20-30% 1 repetition maximum [1-RM]) is a novel exercise technique that has been
shown to increase muscle activity (as measured by surface and intramuscular
electromyography [EMG]) to levels greater than light-load resistance exercise (LLRE)
without BFR (Moritani et al., 1992, Yasuda et al., 2006), while being similar to
traditional heavy-load resistance exercise (HLRE; ≥ 65% 1-RM) (Takarada et al.,
2000c, Yasuda et al., 2008). An increase in muscle activation during BFR-RE indicates
a modification in the orderly recruitment of motor units to include fast-twitch muscle
fibres despite the use of light-loads (Moritani et al., 1992). The increase in EMG
amplitude has been speculated to be related to a number of factors including; i) pooling
of blood distal to the cuff (Iida et al., 2007); ii) an increase in accumulation of
metabolites within muscle such as blood lactate (Yasuda et al., 2012a); iii) altered
availability of metabolic substrates such as oxygen, glucose, and free fatty acids
(Moritani et al., 1992, Suga et al., 2012); or a combination of these. In any case, it is
most likely that the ischemic/hypoxic environment associated with BFR-RE alters
sensory feedback via group III and IV muscle afferents to modify muscle activation
(Yasuda et al., 2010a).
Since voluntary muscle activity arises from the level of the human primary motor cortex
(M1), it is reasonable to hypothesise that during BFR-RE there may be some form of
modulation within M1 that alters the pattern of motor unit recruitment (Nolte, 2002,
Rothwell, 1994). Currently, information regarding neuromuscular function during BFR-
RE or the post-exercise time course response to this type of exercise remains limited
(for review, see Karabulut et al., (2007b)). As discussed, previous studies have reported
increases in surface and/or intramuscular EMG (Moritani et al., 1992, Takarada et al.,

117
2000c, Yasuda et al., 2008, Yasuda et al., 2006), while two studies have utilized the
twitch interpolation technique to determine muscle activation levels (Karabulut et al.,
2010b, Moore et al., 2004). Furthermore, using near infrared spectroscopy it was
observed that unilateral elbow flexion exercise (20% 1-RM) with BFR (130% systolic
blood pressure; 130-170 mmHg) increased cerebral blood flow to a greater extent than a
non-BFR control, suggesting that the contralateral M1 was activated to a greater
magnitude during an acute resistance exercise bout in combination with BFR (Morita et
al., 2010). It is important to note that these are peripheral measures of neuromuscular
activity, and not a direct measure of the corticomotor structures involved in modulating
voluntary force production. Therefore, a limitation of the current BFR-RE data is that it
provides no information regarding the output from the M1.
Corticomotor excitability and inhibition can be examined using transcranial magnetic
stimulation (TMS) to measure the change in amplitude of motor evoked potentials
(MEPs) recorded via EMG from the target muscle (Terao and Ugawa, 2002). When
normalized to a peripheral nerve stimulus, a modification in the amplitude of MEPs
following an intervention reflect the excitability of corticomotor and spinal
motoneurons (Terao and Ugawa, 2002). While no study has used TMS following BFR-
RE to examine corticomotor excitability, there is some evidence to suggest that
corticomotor excitability and twitch force are modified following acute bouts of
resistance exercise under normoxia (Carroll et al., 2008, Selvanayagam et al., 2011) and
systemic hypoxic conditions (Millet et al., 2012). Further evidence of modifications in
corticomotor excitability and inhibition has been observed in response to temporary
ischemic nerve deafferentation (Brasil-Neto et al., 1993a, Brasil-Neto et al., 1993b,
Ridding and Rothwell, 1995). However, it is important to note that these studies did not
use an exercise intervention, and only examined corticomotor excitability and inhibition

118
under resting ischemic conditions. For example, to induce complete ischemic nerve
block of the hand muscles (31.7 ± 3.8 min), a tourniquet was applied across the elbow
at a pressure of 125-130% resting systolic blood pressure (200-250 mmHg) (Ziemann et
al., 1998a). MEP amplitudes of muscles proximal to the tourniquet (biceps brachii and
deltoid) measured during the late onset of ischemia increased by approximately 30%
when normalized to baseline, and was approximately 60% greater at 20 minutes post-
ischemia. Interestingly, MEP amplitude remained elevated for at least 60 minutes
following deflation of the tourniquet (Ziemann et al., 1998a). The increase in MEP
amplitude likely reflects a change in the excitability or representation of these muscles
at the level of the M1, given that measurement of spinal excitability assessed via
transcranial electrical stimulation and Hoffmans reflex remain unchanged (Brasil-Neto
et al., 1993b). The increase in MEP amplitudes observed are suggested to be mediated
by the strengthening (e.g. long term potentiation) or weakening (e.g. long term
depression) of pre-existing synaptic connections (Ziemann et al., 1998b), or the removal
of local inhibition of corticomotor neurons that are responsible for movement in the
target muscle proximal to the external pressure cuff (Ziemann et al., 1998a).
Given that corticomotor inputs are required for motor unit recruitment (Nolte, 2002,
Rothwell, 1994), it seems plausible to suggest that during BFR-RE there may be some
form of modulation within the M1 that alters the pattern of motor unit recruitment.
Therefore, the purpose of this study was to investigate whether an acute bout of BFR-
RE of the biceps brachii differentially modulated corticomotor excitability and short-
interval intracortical inhibition (SICI). Specifically, we examined whether any changes
in corticomotor excitability and SICI were different between BFR-RE and more
traditional training methods such as HLRE and LLRE. In addition, due to variations in
published techniques to apply BFR (e.g. the duration of restriction and applied

119
exercising cuff pressure) that may affect responses to exercise with BFR (Fahs et al.,
2012), the present study also compared two common protocols to conduct BFR-RE
(continuous and intermittent BFR application). It was hypothesized that an acute bout of
BFR resistance exercise of the biceps brachii would rapidly modulate elements of
corticomotor plasticity, as reflected by changes in corticomotor excitability and SICI.

120
4.2 Methods
4.2.1 Participants
Ten (n = 10) male participants (22 ± 2 years; 178.5 ± 6.8 cm; 71.6 ± 6.3 kg) volunteered
to take part in the study, and provided written informed consent to the experimental
procedures prior to participation. All participants in this study were recruited in
accordance with the general methods employed in chapter three; section 3.1 (page 97).
4.2.2 Experimental design
Figure 4.1 outlines the organisation of the study. Prior to beginning the study,
participants underwent a familiarisation session that involved; (i) anthropometric
measurements; (ii) strength testing to evaluate maximal voluntary dynamic elbow flexor
muscle strength (1-RM); (iii) blood pressure assessment and BFR protocol, and (iv)
familiarisation of all TMS testing procedures. Following this visit, in a balanced
randomized crossover design, participants attended the laboratory on four separate
occasions, each separated by at least 7 days. At each visit, participants completed one of
four resistance exercise trials. The four trials were heavy-load resistance exercise (HL),
light-load resistance exercise (LL), and two BFR trials; one where the pressure was
applied continuously throughout the duration of the exercise bout including rest periods
(BFR-C) and the other whereby the pressure was applied intermittently during exercise
only (BFR-I). Participants were instructed to avoid caffeine, medications, and exercise
on the day of testing. All four visits to the laboratory were at the same time of day. Prior
to beginning each trial (Baseline), MEPs were recorded for single- and paired-pulse
TMS and was applied to the M1 contralateral to the exercised biceps brachii (Figure
4.2). Single- and paired-pulse TMS was conducted again four times post-exercise. The

121
first set of data was collected 5 min post-exercise to avoid the period when muscle
effects are largest (i.e. post-exercise MEP depression/facilitation (Brasil-Neto et al.,
1993a)), then again at 20 min, 40 min, and at 60 min post-exercise. Direct muscle
responses (MMAX) were obtained from the biceps brachii by supramaximal electrical
stimulation of the brachial plexus (Erb’s point) under resting conditions prior to TMS at
all-time points. All data (single- and paired-pulse TMS, as well as MMAX) were
collected with the participant in a seated position, while the resistance exercise trials
were performed with the participant standing.

122
Figure 4.1 Organisation of the study. 1-RM, one repetition maximum; AMT, active motor threshold; BFR-C, continuous blood flow restriction; BFR-I, intermittent
blood flow restriction; CS, conditioning stimulus; HL, heavy-load resistance exercise; ISI, interstimulus interval; LL, light-load resistance exercise; rmsEMG, root
mean square of the electromyography.
122

123
4.2.3 Maximal dynamic strength testing
Please refer to chapter three, and section 3.4.1 (page 101) for a detailed description of
the methods employed for 1-RM testing. To establish the exercising load used during
each trial, participants performed a standard unilateral elbow flexion 1-RM test as
previously described (Munn et al., 2005). Briefly, a starting weight was chosen based
on participant-estimated strength. With elbow in full extension, forearm supinated, and
the opposite arm placed behind the back while standing against a wall to prevent
excessive body movement, participants performed elbow flexion (biceps curl) to lift the
dumbbell through a full range of motion.
4.2.4 Resistance exercise trials
In all trials participants performed supervised unilateral elbow flexion/extension
exercise (i.e. a standard series of dumbbell biceps curls) to a repetition timing
monitored by a metronome (2 s concentric; 2 s eccentric). The sets/reps regimen for all
trials was according to standard protocols to conduct each type of exercise (Fahs et al.,
2012). For HL, participants completed four sets (6-8 repetitions; 80% 1-RM) with 2.5
min rest between sets. For LL, BFR-C and BFR-I, participants completed a set of 30
repetitions followed by three sets of 15 repetitions (20% 1-RM) with 30 seconds rest
between sets. Table 4.1 describes the workload characteristics and BFR pressures for all
trials. The total time to complete HL was 9 min, whereas all other trials were 6.5 min.
The average relative work of exercise (total reps x relative load (i.e. 0.2 for 20% 1-RM
and 0.8 for 80% 1-RM; mean ± SD) was 23 ± 3 for HL, which was approximately 1.5
fold greater when compared with all other trials (15 ± 0 for LL; 15 ± 1 for both BFR-C
and BFR-I).

124
Table 4.1 Maximum strength (1-RM) and exercise workload characteristics for each trial.
TRIAL 1-RM Load (kg) Sets (Reps)
Restriction pressure
(%SBP) (mmHg)
1-RM 17.5 ± 1.2 kg
HL 80% 14.1 ± 1.0 4 (6-8)
LL 20% 3.5 ± 1.0 4 (30, 15, 15, 15)
BFR-C 20% 3.5 ± 1.0 4 (30, 15, 15, 15) 80 94 ± 4
BFR-I 20% 3.5 ± 1.0 4 (30, 15, 15, 15) 130 153 ± 5
1-RM, one repetition maximum; BFR-C, continuous blood flow restriction; BFR-I, intermittent
blood flow restriction; HL, heavy-load resistance exercise; LL, light-load resistance exercise;
SBP, systolic blood pressure. Data reported as Mean ± SEM.
4.2.6 Blood flow restriction protocol
For this study the BFR pressures were set according to the method described in chapter
three, and section 3.3 (page 98). The final exercise pressure used during BFR-C and
BFR-I were set according to each participants’ brachial systolic BP which was taken on
their exercising (dominant) arm with the participant in a standing position. The final
exercise pressures equated to 80% systolic BP for BFR-C and 130% systolic BP for
BFR-I, which was equal to 94 ± 4 mmHg and 153 ± 5 mmHg, respectively (Table 4.1).
For BFR-I only, the cuff was completely deflated (i.e. 0 mmHg) during the rest periods
between sets. This deflation was performed to improve participant comfort and
tolerance, and is a method of BFR application used previously (Cook et al., 2007, Kacin
and Strazar, 2011, Suga et al., 2012, Wernbom et al., 2006).

125
4.2.7 Electromyography and transcranial magnetic stimulation
Electromyography and TMS measurements were examined according to the methods
employed in chapter three, and section 3.5 (page 107). In addition, specifically to this
study, surface EMG was recorded from the biceps brachii muscle of the exercised
(dominant) arm, using 9 mm cup electrodes (Electrode model: MLAWBT9,
ADInstruments, Bella Vista, Australia). Two electrodes were placed over the muscle
belly of the biceps brachii, and one reference electrode was positioned on the
participants’ hand (Figure 4.2). The single-pulse TMS protocol for MEP amplitude
included 10 unconditioned stimuli elicited at a stimulus intensity of 130% AMT. For
paired-pulse TMS stimulation to induce SICI, the pair of stimuli consisted of a
subthreshold conditioning stimulus at 70% AMT, followed by a suprathreshold test
stimulus at 130% AMT. The interstimulus interval was 3 ms. For each trial, the
intensities used for single- and paired-pulse TMS were determined at baseline. If
required, the stimulus intensity was adjusted at each time-point post-exercise for each
trial if there was a change in AMT. Each stimulus was delivered in random intervals
every five to 12 sec to avoid stimulus anticipation, and 60 sec rest was provided
between the single- and paired-pulse stimuli to reduce the possibility of muscle fatigue.
4.2.7.1 Active motor threshold
All stimuli were delivered during a low level contraction of the biceps brachii, which
were performed by supinating the hand and maintaining 90 degrees of elbow flexion. In
order to quantify the appropriate level of muscle contraction during TMS testing,
participants completed a maximal voluntary isometric contraction (MVIC) of the
dominant biceps brachii. Participants stood in the anatomical position, with the hand
supinated and maintaining 90 degrees of elbow flexion. The researcher placed an

126
adjustable weighted dumbbell in the palm of their hand. Participants were instructed to
grasp the dumbbell and maintain 90 degrees of elbow flexion for three seconds, without
movement of the abdomen or altering their posture. The maximal load that could be
held static with correct technique served as their MVIC. Maximal root mean squared
electromyography (rmsEMG) for the biceps was obtained during the three second hold
of their MVIC. During all subsequent TMS testing, holding the arm in this joint
position without resistance equated to 3.93 ± 0.40% of the maximal rmsEMG, with
consistent low level muscle activation confirmed by recording pre-stimulus rmsEMG
for the 100 ms epoch prior to the delivery of each stimuli. AMT was established as the
stimulus intensity at which a small MEP (200 µV in 3 out of 5 consecutive trials) during
a low level isometric contraction of the biceps brachii at 3.93 ± 0.40% maximal
rmsEMG activity (Wilson et al., 1993).
4.2.7.2 Motor evoked potentials and short-interval intracortical inhibition
Both MEP amplitude and SICI were collected according to the procedures described in
the general methods in chapter three, and section 3.5.4 (page 109). In addition,
specifically to this study, a 70 mm figure 8 coil (external loop diameter of 9 cm) was
used. The handle of the TMS coil was positioned over the “optimal” site (the location
on the M1 that evokes the maximum MEP amplitude to the muscle of interest), and
oriented so that the axis of the intersection between the two loops was oriented at
approximately 45 degrees to the sagittal plane (Figure 4.2). This arrangement induced a
posterior-anterior current flow across the motor strip for activating the dominant M1
and right biceps brachii muscle (Kidgell et al., 2010).

127
Figure 4.2 Visual representation of the experimental set up for TMS testing. a represents the
placement of the figure of eight coil (70 mm), held tangential to the skull in an anterior-
posterior orientation, so that the current activated the left M1 (right-side muscles). In addition,
the participant is wearing the fitted cap with markings of 1 cm distance in both anterior-
posterior and medial-lateral directions; b represents the paired-pulse magstim; c represents
visual feedback on the computer monitor, and; d represents the electrode placement on the
muscle belly of the biceps brachii and one reference electrode over the participants’ hand.
4.2.7.3 Maximal compound muscle action potential
For a more detailed description of the general methods employed, refer to chapter three,
and section 3.5.5 (page 109). In addition, specifically to this study, MMAX was obtained
from the right biceps brachii by supramaximal percutaneous electrical stimulation of the
brachial plexus (Erbs point). Each electrical pulse delivered via the Digitimer was done
via positioning bipolar electrodes in the supraclavicular fossa. The stimuli were
delivered while the participant sat in an upright position, with the arm resting
comfortably in the lap, producing no detectible background EMG. An increase in
current strength was applied to the brachial plexus until there was no further increase in
the amplitude of surface EMG response (MMAX).
a
b
c
d

128
4.2.8 Data analyses
Pre-stimulus rmsEMG activity was determined in the biceps brachii 100 ms prior to
each TMS stimulus during each condition. Any pre-stimulus rmsEMG that exceeded 5
± 3% of maximal rmsEMG were discarded and the trial repeated. The peak-to-valley
amplitude of MEPs evoked as a result of stimulation was measured in the biceps brachii
muscle contralateral to the cortex being stimulated in the period 10-50 ms after
stimulation. MEP amplitudes were analysed using LabChart software (8,
with a cursor, providing peak-to-valley values in μV and were then normalized to
MMAX. Average MEP amplitudes were obtained separately for single- and paired-pulse
TMS for each stimulation block (20 trials for each time point). SICI was calculated
using the following equation: (1 – PP/SP) x 100. This calculation, adapted from
(Lackmy and Marchand-Pauvert, 2010), has a direct relationship with SICI (unlike the
traditional method for calculating SICI ratio). For example, a decrease in inhibition
following the intervention would be depicted by a decrease in the numerical value.
4.2.9 Statistical analysis
All data were screened for normality using Shapiro-Wilk and Kolmogorov-Smirnov
tests, and were found to be normally distributed. Consequently, a repeated measures
ANOVA for within factors of trial (HL, LL, BFR-C and BFR-I) and time (Baseline, 5
min post, 20 min post, 40 min post and 60 min post) was used to examine the trial and
time effects on rmsEMG, AMT, MEP amplitude, SICI, and MMAX. When appropriate,
post-hoc (Tukey) analyses for pairwise comparisons of means were used when
significant interactions were found. For all tests, the Huynh-Feldt correction was
applied if the assumption of sphericity was violated. Alpha was set at P ≤ 0.05, and all

129
results are displayed as mean ± standard error of the mean (SEM) unless stated
otherwise.

130
4.3 Results
4.3.1 Baseline characteristics and strength
There were no differences in AMT, MMAX, MEP amplitude, SICI, and rmsEMG
between trials at baseline (all P ≥ 0.05). In addition, the mean TMS stimulator output
for AMT, single-pulse, paired-pulse and MMAX were not different between trials or time
points, therefore these were averaged across all trials and are presented in Table 4.2.
Mean elbow flexion 1-RM strength was 17.6 ± 3.9 kg. The exercise weight for the HL
condition was 14.1 ± 3.1 kg. For LL, BFR-C, and BFR-I, the exercise weight was 3.5 ±
0.8 kg.
Table 4.2 Baseline corticomotor responses and TMS variables.
TMS variables
MMAX (mV) 11.92 ± 1.52
Stimulator output for MMAX (mA) 62.50 ± 13.50
AMT (mV) 0.33 ± 0.10
AMT (% MSO) 39.4 ± 2.0
Unconditioned (single-pulse; % MSO) 51.2 ± 2.7
Conditioning (paired-pulse; % MSO) 27.5 ± 1.5
Maximal rmsEMG (mV) 1.62 ± 0.20
AMT, active motor threshold; Maximal rmsEMG, maximal root mean squared
electromyography; MMAX, maximal compound peripheral muscle action potential, MSO;
maximal stimulator output. Data reported as Mean ± SEM.

131
4.3.2 Pre-stimulus rmsEMG and MMAX
The averaged pre-stimulus rmsEMG values recorded were not different between groups
at baseline. In addition, there were no significant differences between trials or time-
points, and therefore no time-by-trial interactions were detected for rmsEMG for the
100 ms prior to stimulation (all P ≥ 0.05). Similarly, for MMAX, there were no time-by-
trial interactions, main effects for time or trial detected (all P ≥ 0.05; Figure 4.3).
Figure 4.3 MMAX amplitude following resistance exercise. HL (heavy-load resistance exercise);
LL (light-load resistance exercise); BFR-C (blood flow restriction with continuous inflation of
cuff pressure); BFR-I (blood flow restriction with intermittent inflation of cuff pressure).

132
4.3.3 Active motor threshold and corticomotor excitability
TMS stimulus output required to evoke AMT for biceps brachii was not different
between trials (Table 4.2). Similarly, AMT was not different between trials at baseline.
Therefore, AMT was averaged across all trials.
Overall, a significant time-by-trial interaction was detected for corticomotor excitability
(Figure 4.4; F12, 108 = 4.223; P ≤ 0.001). Univariate post hoc analyses revealed a
significant increase in MEP amplitude at 5 min post-exercise following LL (P ≤ 0.001),
BFR-I (P ≤ 0.001), and BFR-C (P ≤ 0.001) relative to HL. In addition, MEP amplitude
was significantly greater following BFR-C compared with LL (P ≤ 0.01) and BFR-I (P
≤ 0.05). MEP amplitude increased rapidly at 5 min post compared with baseline
following all trials except for HL (P ≤ 0.001). At 20 min post-exercise, the magnitude
of the increase in MEP amplitude remained significant for LL (P ≤ 0.01), BFR-I (P ≤
0.001), and BFR-C (P ≤ 0.001) compared with HL. Furthermore, MEP amplitude
remained significantly elevated following BFR-C compared with LL (P ≤ 0.001) and
BFR-I (P ≤ 0.05). Relative to baseline, MEP amplitude remained significantly greater
20 min post-exercise following all trials (P ≤ 0.01) except HL. Similarly, at 40 min
post-exercise, MEP amplitude remained significant for BFR-C compared with HL (P ≤
0.001), LL (P ≤ 0.001), and BFR-I (P ≤ 0.001). In addition, MEP amplitude was greater
for LL and BFR-I compared with HL (P ≤ 0.05). Relative to baseline, MEP amplitude
remained elevated following both BFR-I (P ≤ 0.01) and BFR-C (P ≤ 0.001) only.
Interestingly, at 60 min post-exercise, MEP amplitude was still significantly elevated
following BFR-C relative to HL (P ≤ 0.001), LL (P ≤ 0.01) and BFR-I (P ≤ 0.001), but
there were no differences between any other trials. MEP amplitude remained
significantly elevated above baseline for BFR-C only (P ≤ 0.001).

133
Figure 4.4 MEP amplitude relative to MMAX following resistance exercise. HL (heavy-load
resistance exercise); LL (light-load resistance exercise); BFR-C (blood flow restriction with
continuous inflation of cuff pressure); BFR-I (blood flow restriction with intermittent inflation
of cuff pressure).
* indicates significantly different to Baseline (P ≤ 0.05).
a indicates significantly different to all others trials (P ≤ 0.05).

134
4.3.4 Short interval intracortical inhibition
Table 4.2 displays mean (± SEM) conditioning stimulus intensity required to evoke
SICI for the biceps brachii for each trial. There were no differences in conditioning
stimulus output required between each trial.
There were no time-by-trial interactions (Figure 4.5; F12, 108 = 1.485; P = 0.014), main
effects for time (F4, 36 = 2.518; P = 0.058) or trial (F3, 27 = 1.182; P = 0.335).
Figure 4.5 SICI amplitude following resistance exercise. HL (heavy-load resistance exercise);
LL (light-load resistance exercise); BFR-C (blood flow restriction with continuous inflation of
cuff pressure); BFR-I (blood flow restriction with intermittent inflation of cuff pressure).

135
4.4 Discussion
The main findings of the present study were; (i) overall, the increase in MEP amplitude
of the biceps brachii was greater following BFR-C compared with all other trials, and
remained so for up to 60 minutes post-exercise; (ii) both BFR trials rapidly increased
corticomotor excitability, (iii) MEP amplitude was unaffected by traditional heavy-load
resistance exercise; and (iv) no modifications were detected for SICI post-exercise
following all trials. These results support our hypothesis, and suggest that in order to
induce rapid and long-lasting increases in corticomotor excitability during BFR-RE of
the biceps brachii, continuous low-pressure application is preferential to intermittent
high-pressure application.
Currently, there is limited data available that has assessed neuromuscular function in
response to BFR-RE. Several studies have reported acute changes in peripheral
measures of the neuromuscular system, such as increases in surface EMG during BFR-
RE (Moritani et al., 1992, Takarada et al., 2000c, Yasuda et al., 2008, Yasuda et al.,
2006), or utilizing the twitch interpolation technique to determine changes in muscle
activation levels following training (Karabulut et al., 2010b, Moore et al., 2004).
However, the present study is the first to directly measure the potential cortical
structures involved in modulating corticomotor excitability and inhibition following
BFR-RE. It was observed that MEP amplitude increased rapidly (at 5 minutes post-
exercise) following BFR-RE regardless of the pattern/timing of restriction and final
inflation pressure. However, MEP amplitude was facilitated for 60 minutes following
BFR-C, but returned to baseline by 40-minutes post-exercise for BFR-I. These results
suggest that the pattern/timing of cuff restriction application during BFR-RE is an
important factor in modulating corticomotor excitability. One potential limitation to the
current study was that we did not include a BFR only (no exercise) trial. Nevertheless,

136
Ziemann et al., (1998a) has previously examined similar time-course corticomotor
responses during and following ischemic nerve deafferentation, and showed that while
corticomotor excitability was increased during the late stage of ischemia (approximately
five minutes after nerve block was achieved at 31.7 ± 3.8 mins), and for 60 minutes
post-ischemia, the increase from baseline was only significant at 20 minutes post-
ischemia (~60% increase). Reduced oxygen availability has been suggested to be a
potential mechanism behind the increased EMG activity seen during BFR-RE (Yasuda
et al., 2010a). However, under systemic hypoxic conditions, MEP amplitude has been
shown not to increase at rest within 60 minutes of exposure (Goodall et al., 2014, Rupp
et al., 2012). In addition, no effect for SICI has been found at rest under systemic
hypoxic conditions (Rupp et al., 2012), or during and following ischemic nerve
deafferentation (Ziemann et al., 1998a). Given that the duration of BFR in the current
study was less than 10 minutes, and restriction of blood flow for this duration without
exercise is not known to induce muscular adaptations, it is not expected that any
changes in corticomotor excitability or inhibition would occur in a BFR only control
trial of this short duration. Therefore, we are confident that our results are likely to be as
a result of the combination of BFR and light-load resistance exercise. Based on this
finding, we propose that when elbow flexion exercise is performed with 20% 1-RM, the
application of low-pressure continuous BFR should be used in order to induce the
greatest modification in corticomotor excitability. Future studies should examine if
similar responses would be observed during muscular contractions at higher intensities,
or for other resistance exercises (e.g. for the lower-body).
Of particular interest to this study was the effect of BFR-RE on modulating
corticomotor excitability and inhibition in comparison with more traditional resistance
exercise techniques. We found no change in corticomotor excitability following the HL

137
trial, which was somewhat unexpected. MEP amplitude has been observed to increase
during sustained isometric contractions of the elbow flexors (Sacco et al., 1997), as well
as following acute bouts of ballistic resistance exercise of small hand muscles (Carroll
et al., 2008, Selvanayagam et al., 2011). In contrast, and in agreement with results from
the current study, no change in MEP amplitude was reported following exercise of the
hand muscles at 80% MVIC (Hortobágyi et al., 2011), or following five sets of 6-10
repetitions of the elbow flexors (load not reported) (Jensen et al., 2005). It is possible
that MEP amplitude did not change following the HL trial due to central fatigue
mechanisms (Gandevia, 2001). While maximal force was not measured post-exercise in
order to determine the level of muscular fatigue, because no change in SICI or MMAX
was observed, we hypothesize that MEP amplitude was not modified in the current
study (and others e.g. Jensen et al., 2005), due to the limited centrally challenging
nature of the HL trial. For example, while the heavy-loads utilized could be considered
challenging to the neuromuscular system, the addition of completing each repetition to
external pacing (i.e. with a metronome) has been shown to increase the complexity of
the movement resulting in increased MEP amplitude following motor skill learning
tasks (Jensen et al., 2005) and short-term resistance training programmes (Kidgell et al.,
2010, Weier et al., 2012). However, in the present study some participants were unable
to keep time with the required contraction rate (2 seconds concentric, 2 seconds
eccentric) due to the heavy-load. As such, this may have limited the centrally
challenging nature of the HL trial, and so may explain why we did not observe any
acute modulation in MEP amplitude. In contrast, in the present study during the LL trial
using the same external pacing as HL, we observed a rapid increase in MEP amplitude
that remained elevated 20 minutes post-exercise. These data suggest that either the load
used during LL did not induce fatigue thus no depression in post-exercise MEP
amplitude, or that the combination of exercise to external pacing and a higher number

138
of repetitions was responsible for the increase in MEP amplitude. Moreover, using the
same light-load resistance exercise and repetition timing but with an applied BFR, we
observed an even larger increase in MEP amplitude, and a longer lasting facilitation of
MEP amplitude post-exercise when compared with both HL and LL trials. Therefore,
the net increase in corticomotor excitability seen in the present study not only provides
support for benefits of BFR-RE in healthy populations, but may also be important for
clinical populations that require increased motor function such as the elderly, stroke
patients, and following musculoskeletal injury.
It is well documented that large motor units (and their associated fast-twitch muscle
fibres) are preferentially recruited during BFR-RE with light-loads (Moritani et al.,
1992, Karabulut et al., 2007, Takarada et al., 2000c, Yasuda et al., 2010a, Yasuda et al.,
2006). This increase in muscle activation during BFR-RE is similar to heavy-load
resistance exercise, and greater than light-load resistance exercise without BFR
(Moritani et al., 1992, Takarada et al., 2000c, Yasuda et al., 2006). It has been proposed
that the high levels of external compression, reduced blood flow, and ischemic/hypoxic
intramuscular environments may all play a role in stimulating the increase in muscle
activation via group III and IV muscle afferents (Moritani et al., 1992, Karabulut et al.,
2007, Yasuda et al., 2010a). Given that sensory feedback to cortical and/or subcortical
areas during exercise and under ischemic/hypoxic conditions has been proposed to alter
muscle activation and corticomotor excitability (Christie and Kamen, 2013, Gandevia et
al., 1996), evidence from the present study further supports a potential role of group III
and IV muscle afferents in modulating corticomotor excitability with BFR. While there
is also evidence to suggest that sensory feedback from group III and IV muscle
afferents plays a role in altering cortical inhibition (Christie and Kamen, 2013), SICI
remained unchanged in the present study following all trials. Previous investigations of

139
SICI on corticomotor plasticity and performance have produced varying results.
Ischemia alone has been shown to produce non-significant reductions in SICI (Ziemann
et al., 1998a), while SICI has also been shown to decrease following resistance exercise
and other motor tasks with increasing levels of force (Rantalainen et al., 2013). In
contrast, several studies show SICI to be unchanged as a result of motor skill practice
(Rosenkranz and Rothwell, 2006, Schmidt et al., 2011), which supports the findings of
the present study in all trials. This suggests that M1 inhibition may not be a primary
factor involved in the use dependant modification observed in the M1 following BFR-
RE, but seems more likely a result of intracortical facilitation.
The resultant increase in MEP amplitude observed following BFR-C suggest
hyperexcitability of excitatory corticospinal circuits, which may lead to long-lasting
adaptations if the intervention is repeated during a training programme, similar to those
observed following heavy-load resistance training (Kidgell et al., 2010, Weier et al.,
2012). However, it is not known whether the increased corticomotor excitability has
any functional outcome such as an increase in muscular strength. Therefore, future
studies investigating the neuromuscular adaptations following BFR-RT using TMS
should do so over short- and long-term training durations. We postulate that the
increase in MEP amplitude of the biceps brachii in the present study was caused by
changes in synaptic efficacy and/or transmission along the corticospinal pathway
following BFR-RE. The rapid and long-lasting modulation of MEP amplitude
potentially reflects a change in the excitability or representation of the biceps brachii at
the level of the M1 because we observed no change in MMAX, which indicates that
peripheral mechanisms were not responsible for this modification. Furthermore,
evidence from ischemic nerve deafferentation shows no change in spinal excitability
using transcranial electrical stimulation or Hoffman reflex (Brasil-Neto et al., 1993b,

140
Ridding and Rothwell, 1995). Although our results support this work, we accept that
changes in MEP amplitude and SICI are not only affected by the excitability of the M1,
but also the excitability of other cortical structures, the brain stem, spinal cord, and the
lower motoneuron pool (Carroll et al., 2001, Classen et al., 1998). Therefore, a
limitation of the current study was that because we did not obtain any measurements at
levels other than the M1, it is therefore possible that changes here may also have
contributed to the observed alterations in MEP amplitude. Another limitation of the
current study was that active MEPs were collected during a low level contraction (3.93
± 0.40% of maximal rmsEMG) and were normalized to MMAX values that were
collected during muscle relaxation. This variation in muscle activation may prevent the
accurate determination of corticomotor excitability and SICI, and should be considered
in future studies. Finally, while the method for measuring SICI has been used
previously to measure changes in intracortical inhibition following resistance training
and motor control tasks (Rantalainen et al., 2013), due to the selected timing and
number of time points for measurement post-exercise within the current study design, it
was not possible to examine SICI in response to a range of test stimulus intensities.
While such an approach may potentially skew our measures of SICI, we think this is
unlikely.

141
4.5 Conclusion
In conclusion, this was the first study to examine corticomotor excitability and
inhibition following an acute bout of BFR-RE. It was demonstrated that corticomotor
excitability increased rapidly following BFR-RE and remained facilitated for up to 60
minutes. Interestingly, we found the increase in corticomotor excitability to be greatest
following a continuous BFR protocol in comparison with an intermittent BFR protocol
and traditional resistance exercise techniques. It is likely that the change in corticomotor
excitability was mediated by altered sensory feedback to cortical and/or subcortical
areas via group III and IV afferent fibres. This effect may contribute to similar longer-
term cortical adaptations that are observed following chronic resistance training with
heavy-loads; however this remains to be elucidated. Therefore, future investigations are
needed to clarify the impact of these corticomotor adaptations on muscle strength and
overall function following BFR-RT in order to better understand the neuromuscular
adaptations that occur following training.

142
CHAPTER FIVE:
Haemodynamic responses to an acute bout of
blood flow restriction resistance exercise
Adapted from:
Brandner CR., Kidgell DJ., and Warmington SA.
Unilateral biceps curl hemodynamics: Low-pressure continuous vs high-pressure
intermittent blood flow restriction. Scand J Med Sci Sports 2014; 25(6).
doi:10.1111/sms.12297

143
5.1 Introduction
Resistance exercise training with light-loads (20-30% one-repetition maximum [1-RM])
in combination with blood flow restriction (BFR) develops both muscle strength and
mass over that of light-load resistance exercise (LLRE) training without BFR (Abe et
al., 2012, Fahs et al., 2012, Loenneke et al., 2011c). These improvements have also
been shown to be equivalent to those achieved with traditional training using heavy-
load resistance exercise (HLRE; ≥ 65% 1-RM) (Clark et al., 2010, Karabulut et al.,
2011a, Laurentino et al., 2012, Takarada et al., 2000c, Thiebaud et al., 2013a).
Consequently, due to the lower mechanical stress on the musculoskeletal system, BFR
resistance exercise (BFR-RE) and training (BFR-RT) may provide a unique method for
potential use by some clinical and elderly populations where HLRE is not possible or
not recommended (Karabulut et al., 2010a, Karabulut et al., 2011a, Takarada et al.,
2000c, Vieira et al., 2012). With this in mind, and despite the effects of BFR-RT on
increasing muscle strength, mass, and endurance being well founded (Abe et al., 2012,
Pope et al., 2013), it is important to identify the haemodynamic effects of BFR-RE to
further establish and support its safe application prior to making any recommendations
for prescription in populations where HLRE may be contraindicated. Of importance is
the method by which BFR may be applied. Techniques vary with respect to factors such
as the type of restrictive cuff (size and material), and the magnitude, timing and
duration of the applied restriction (Fahs et al., 2013a, Fahs et al., 2012, Loenneke et al.,
2011c, Loenneke et al., 2013a). Therefore, it is important to examine the
haemodynamic responses to different methods of BFR application in order to evaluate
the parameters that limit haemodynamic stress, and as a consequence would seem most
suitable for guiding prescription in ‘at risk’ populations.

144
BFR-RE is most commonly applied continuously throughout an entire exercise bout
including the rest periods (Clark et al., 2010, Hollander et al., 2010, Karabulut et al.,
2010a, Patterson and Ferguson, 2010). An alternative is to apply an intermittent
restriction whereby cuff deflation occurs during the inter-set rest periods (Cook et al.,
2007, Evans et al., 2010, Kacin and Strazar, 2011, Laurentino et al., 2008). Our
laboratory has previously observed (unpublished) that unilateral elbow flexion exercise
(20% 1-RM) using a relatively wide cuff (14 cm) was not well tolerated by participants,
with most being unable to complete the exercise requirements when BFR was applied
continuously using pressures equal or greater than resting systolic blood pressure (BP;
~120 mmHg). In contrast, all participants were able to complete the exercise during
intermittent application of the restriction, and this was despite the use of higher
pressures up to the maximum pressure tested (130% of systolic BP; ~155 mmHg).
While individualized selection of restriction pressures may be preferential (Downs et
al., 2014, Loenneke et al., 2011c, Loenneke et al., 2013a), and albeit also dependent on
cuff width (Rossow et al., 2012), it appears that when using relatively wide cuffs for
continuous BFR-RE that low-pressures should be used (≤ systolic BP; i.e. 90-100
mmHg), whereas higher pressures (≥ systolic BP; i.e. 150-160 mmHg) could be used
during intermittent application.
While the chronic muscular adaptations (increased muscle strength and mass) to BFR-
RE have been characterised (Loenneke et al., 2011f, Pope et al., 2013, Wernbom et al.,
2008), the acute haemodynamic responses are less well understood but appear
moderately elevated when compared with LLRE (Hollander et al., 2010, Patterson and
Ferguson, 2010, Takano et al., 2005, Vieira et al., 2012). Cardiac output (Q̇ ) is similar
between load-matched BFR and non-BFR LLRE, yet is derived from an elevated heart
rate (HR) combined with a reduced stroke volume (SV) and venous return during BFR

145
exercise (Takano et al., 2005). In addition, mean arterial pressure (MAP) and systolic
BP during BFR-RE appears elevated in comparison with non-BFR LLRE (Takano et
al., 2005). However, attempts to characterise the acute haemodynamics during standard
BFR-RE methods have typically only compared BFR with non-BFR during LLRE
(Patterson and Ferguson, 2010, Takano et al., 2005, Vieira et al., 2012), with no direct
comparisons between BFR-RE, LLRE and HLRE in the same participant group. This is
despite recent reports where measures were taken pre-exercise but only as early as 15
min (Fahs et al., 2011a) and 30 min post-exercise (Rossow et al., 2011). Recently,
Downs et al., (2014) showed that for fatiguing BFR-RE the immediate post-exercise
(within 90 s) HR, Q̇ , and SV were greater during HLRE and LLRE (leg-press and
plantar flexion) when compared with both high- and low-pressure BFR-RE.
Conversely, and of some concern, both systolic BP and diastolic BP were higher during
BFR-RE (range: 140-156 and 67-80 mmHg for systolic BP and diastolic BP,
respectively) compared with HLRE (134 ± 4 and 58 ± 3 mmHg for systolic BP and
diastolic BP, respectively) and LLRE (127 ± 4 and 57 ± 3 mmHg for systolic BP and
diastolic BP, respectively). However, these data seem largely complicated by the
exercise being undertaken to failure, such that less work was performed during BFR-RE
than during a typical BFR protocol where sets comprise an initial 30 contractions
followed by three sets of 15 repetitions (Fahs et al., 2012). Despite being the first study
to compare the haemodynamic responses between continuous high- and low-pressure
BFR-RE and more traditional resistance exercise methods, to our knowledge no study
has assessed the haemodynamic responses between continuous and intermittent BFR-
RE. Moreover, no study has assessed these responses during upper-body resistance
exercise.

146
Therefore, the purpose of this study was to compare the acute haemodynamic responses
to unilateral biceps curl BFR-RE with both HLRE and LLRE in the same young healthy
participants. In addition, we also compared two methods to conduct BFR-RE
(continuous low-pressure and intermittent high-pressure BFR application). It was
hypothesised that the haemodynamic stress of unilateral elbow flexion would be
greatest with HLRE, lowest with LLRE, with responses to BFR-RE residing between
these two more traditional forms of exercise. It was also expected that the intermittent
high-pressure application of BFR during exercise would induce a greater elevation in
haemodynamic stress in comparison with continuous low-pressure BFR, due to the
higher cuff pressure.

147
5.2 Methods
5.2.1 Participants
Twelve (n = 12) recreationally active male participants volunteered to participate in the
study (mean ± SD; 23 ± 3 yrs; 179.9 ± 7.5 cm; 72.6 ± 8.2 kg). All participants in this
study were recruited in accordance with the general methods employed in chapter three;
section 3.1 (page 97). In addition, participants attended the laboratory at the same time
of day to avoid any diurnal influences and refrained from exercise, caffeine, and alcohol
consumption 12 hours before data collection.
Figure 5.1 outlines the organisation of the study. Participants completed an initial
familiarisation session that comprised an assessment of maximal voluntary dynamic
strength of the elbow flexors (1-RM), and measurement of resting haemodynamics.
This included being instructed on the correct technique to undertake a rebreathing
manoeuvre using a closed circuit metabolic system to measure cardiac output (Innocor,
Innovision A/S, Odense, Denmark). Participants were provided with instruction about
the breathing rate, depth and timing required to successfully conduct the test. Following
this, participants attended the laboratory on four separate occasions separated by at least
7 days to complete the exercise trials in a balanced, randomized crossover design. Trials
were 1) heavy load resistance exercise (HL; 80% 1-RM); 2) light-load resistance
exercise (LL; 20% 1-RM); 3) LLRE with a continuous low-pressure BFR (BFR-C; 20%
1-RM); 4) LLRE with an intermittent high-pressure BFR (BFR-I) (Table 5.1). For BFR-
C, cuff pressure was applied continuously throughout the duration of the exercise bout
including inter-set recovery periods. For BFR-I, cuff pressure was applied intermittently
during exercise only, with the cuff inflated prior to every set and released immediately

148
after the final repetition of each set (Suga et al., 2012). Haemodynamic responses for
each trial were measured at rest prior to exercise (Baseline), during exercise (set 2 and
set 4), and at 5, 20, 40, and 60 min post-exercise. All exercise was performed while
standing and used only the dominant limb.
5.2.3 Maximal dynamic strength
Maximal dynamic strength (1-RM) of the elbow flexors was examined as per section
4.2.3 (page 123). Of note, MVIC testing was not a requirement for this study.
5.2.4 Resistance exercise trials
The resistance exercise trials performed in this study were identical to those in chapter
four. For a more detailed description, refer to section 4.2.4 (page 123).
For this study, BFR pressures were set according to the general methods described in
chapter three, and section 3.3 (page 98). Briefly, pressures were set according to each
participants’ brachial systolic BP which was taken on their exercising (dominant) arm
with the participant in a standing position. The final exercise pressures equated to 80%
systolic BP for BFR-C and 130% systolic BP for BFR-I. In this study, the average cuff
pressures used for BFR-C and BFR-I were 91 ± 2 mmHg and 151 ± 4 mmHg,
respectively (see Table 5.1).

149
Figure 5.1 Organisation of the study. 1-RM, one repetition maximum; BFR-C, continuous blood flow restriction; BFR-I, intermittent blood flow restriction; HL,
heavy-load resistance exercise; LL, light-load resistance exercise.
149

150
5.2.6 Haemodynamic measurement
The measurement of all haemodynamic variables were completed according to the
general methods in chapter three, section 3.6 (page 110). See also Figure 5.2 for the
equipment set up for haemodynamic testing during resistance exercise.
Figure 5.2 An example of participant and equipment set up for haemodynamic testing and
resistance exercise. a represents the Zimmer Automatic Tourniquet System (A.T.S) 3000 used
to control the BFR pressure during exercise; b represents the wide BFR cuff used on the
participants dominant limb during exercise; c represents the Innocor metabolic cart, providing
visual feedback and results on the computer monitor, which is measured at d via re-breathing
method; e represents the lead author conducting blood pressure measurement on the participants
non-exercise arm with a standard blood pressure cuff and stethoscope.
5.2.7 Perceptual responses
Both DOMS and RPE were collected according to the methods described in chapter
three, section 3.7 (page 113). In addition, specific to this study, DOMS ratings were
reported according to a previously verified protocol (Chen and Nosaka, 2006) for five
a
b
c
d
e

151
days post-exercise. RPE was assessed 5 minutes post-exercise for each bout using
Borg’s 6-20 RPE scale (Borg, 1998).
A split-plot in time, repeated measures ANOVA was used to compare the
haemodynamic responses for trial (HL, LL, BFR-I and BFR-C) by time (Baseline, set 2,
set 4, and 5, 20, 40 and 60 min post-exercise). In addition, a split-plot in time, repeated
measures ANOVA was also used to compare the DOMS responses for trial (HL, LL,
BFR-I and BFR-C) by time (Baseline, 24 hours, 48 hours, 72 hours, 96 hours, 120
hours post-exercise). For RPE, a one way ANOVA was used to compare the responses
between trials. Where significant interactions were observed, a univariate post-hoc
analysis (Tukeys) for pairwise comparisons was performed. Alpha was set at P ≤ 0.05.
Unless otherwise stated all data are displayed as Mean ± Standard Error of Mean
(SEM).

152
5.3 Results
Mean elbow flexor strength is displayed in Table 5.1, along with the average exercising
load for each trial.
Table 5.1. Maximum strength (1-RM) and exercising workload characteristics for each trial.
TRIAL 1-RM Load (kg) Sets (Reps)
Restriction pressure
(%SBP) (mmHg)
1-RM 17.7 ± 2.3 kg
HL 80% 14.2 ± 1.8 4 (6-8)
LL 20% 3.6 ± 0.5 4 (30, 15, 15, 15)
BFR-C 20% 3.6 ± 0.5 4 (30, 15, 15, 15) 80 91 ± 2
BFR-I 20% 3.6 ± 0.5 4 (30, 15, 15, 15) 130 151 ± 4
1-RM, one repetition maximum; BFR-C, continuous blood flow restriction; BFR-I, intermittent
blood flow restriction; HL, heavy-load resistance exercise; LL, light-load resistance exercise;
SBP, systolic blood pressure. Data reported as Mean ± SEM.
5.3.1 Haemodynamics
All haemodynamic measures (HR, BP, Q̇ , SV and TPR) were not different at baseline
between trials. In addition, all haemodynamic parameters returned to baseline within 5
minutes upon completion of each trial.

153
5.3.1.1 Cardiac parameters
HR increased from baseline during exercise in all trials (Figure 5.3 P ≤ 0.001). This
increase was greatest in HL and BFR-I compared with both LL and BFR-C during set 2
(P ≤ 0.001). During set 4, HR was also higher during HL compared with both LL and
BFR-C (P ≤ 0.001), while also being greater during BFR-I compared with LL (P ≤
0.01) but not BFR-C.
Figure 5.3. Heart rate responses during all four trials.
* indicates significant difference compared with Baseline and all post-exercise measurements
(P ≤ 0.01).
b indicates significant difference compared with LL (P ≤ 0.01).
c indicates significant difference compared with LL and BFR-C (P ≤ 0.05).

154
Q̇ increased from baseline during exercise in all trials (Figure 5.4; P ≤ 0.001) and was
similar between HL, BFR-C, and BFR-I during set 2 and set 4. This increase was
greatest in HL compared with all other trials at set 2 (P ≤ 0.001) and set 4 (P ≤ 0.01),
with no differences observed between LL, BFR-I and BFR-C.
Figure 5.4. Cardiac output responses during all four trials.
(P ≤ 0.01)
d indicates significant difference compared with all other trials (P ≤ 0.05).

155
SV remained unchanged from baseline, and throughout exercise and recovery in all
trials, although during HL, SV tended to increase from baseline to set 2 (P = 0.08)
(Figure 5.5).
Figure 5.5. Stroke volume responses during all four trials.

156
5.3.1.2 Blood pressures
Blood pressures (systolic BP, diastolic BP, and MAP) all increased from baseline to
exercise in all trials (P ≤ 0.001), and returned to baseline again within 5 min upon
completion of exercise (Figures 5.6-5.8). Systolic BP was higher in HL and BFR-I
compared with both BFR-C and LL during set 2 (P ≤ 0.01), and tended to be higher for
BFR-C compared with LL (P = 0.09). Systolic BP increased from set 2 to set 4 for
BFR-C (P ≤ 0.01), and subsequently systolic BP during set 4 was lower in LL
compared with all other trials (P ≤ 0.01).
Figure 5.6 Systolic blood pressure responses during all four trials.
(P ≤ 0.01).
# indicates significant difference compared with Set 2 (P ≤ 0.01).
c indicates significant difference compared with BFR-C (P ≤ 0.05).
d indicates significant difference compared with all other trials (P ≤ 0.05).

157
Diastolic BP during set 2 was higher in HL and BFR-I compared with LL only (P ≤
0.01), but was not different between any other trials. While during set 4, the increase in
diastolic BP from baseline was higher for BFR-I compared with LL only (P ≤ 0.01).
Figure 5.7 Diastolic blood pressure responses during all four trials.
(P < 0.01).

158
MAP during set 2 was higher in HL and BFR-I compared with both BFR-C (P ≤ 0.05)
and LL (P ≤ 0.001). During set 4 MAP remained elevated for HL (P ≤ 0.05) and BFR-I
(P ≤ 0.001) compared with LL, and tended to be higher for BFR-C compared with LL
(P = 0.06).
Figure 5.8 Mean arterial blood pressure responses during all four trials.
(P ≤ 0.01).
c indicates significant difference compared with LL and BFR-C (P ≤ 0.05).

159
5.3.1.3 Total peripheral resistance and rate pressure product
There was a significant time-by-trial interaction (P ≤ 0.001) such that TPR was lower in
HL than all other trials at set 2 (P ≤ 0.05) (Table 5.2). No differences were evident
between trials at any other time point. TPR increased from baseline to set 4 in BFR-I (P
≤ 0.05), and also tended to increase for BFR-C (P = 0.06) and LL (P = 0.054), while
being significantly elevated from baseline in LL at 5 min post-exercise (P ≤ 0.01). No
other differences were evident across time within trials.
There was also a significant time-by-trial interaction such that RPP increased from
baseline during exercise (set 2 and set 4) in all trials (P ≤ 0.001) (Table 5.2). For set 2,
RPP was greater in HL compared with LL (P ≤ 0.01) and tended to be greater than
BFR-C (P = 0.09), but was not different from BFR-I. In addition, at set 2, RPP was
higher in BFR-C and BFR-I compared with LL (P ≤ 0.05). Interestingly, at set 4 RPP
was similar between HL, BFR-C and BFR-I, which were all greater than LL (P ≤ 0.05).

160
Table 5.2. Total peripheral resistance (TPR) and rate pressure product (RPP) responses during
all four trials.
(P ≤ 0.01).
b indicates significant difference to LL (P ≤ 0.05).
d indicates significant difference with all other trials (P ≤ 0.05).
HL LL BFR-C BFR-I
TPR
(% baseline)
Baseline 100 100 100 100
Set 2 84 ± 2d
104 ± 1 106 ± 1 114 ± 1
Set 4 74 ± 5 115 ± 1 117 ± 1 124 ± 4*
5 min post 103 ± 1 118 ± 1* 112 ± 1 108 ± 1
20 min post 101 ± 1 107 ± 1 105 ± 1 104 ± 1
40 min post 101 ± 1 99 ± 1 100 ± 1 102 ± 0
60 min post 94 ± 1 93 ± 1 95 ± 1 103 ± 1
RPP
(% baseline)
Baseline 100 100 100 100
Set 2 186 ± 15*b
138 ± 5* 156 ± 6* 185 ± 7*b
Set 4 217 ± 16*b
142 ± 5*d
187 ± 8* 204 ± 12*
5 min post 111 ± 3 110 ± 4 106 ± 4 101 ± 4
20 min post 104 ± 3 103 ± 3 97 ± 3 101 ± 3
40 min post 95 ± 3 96 ± 3 93 ± 3 98 ± 12
60 min post 93 ± 3 95 ± 3 94 ± 2 93 ± 2

161
There was a significant main effect for trial detected for RPE (Figure 5.9, top; P ≤
0.001). Post hoc analyses revealed that RPE was higher post-exercise for all trials in
comparison with LL (all P ≤ 0.001). In addition, RPE was higher for BFR-I in
comparison with BFR-C (P ≤ 0.01).
With regard to DOMS, there was a significant trial-by-time interaction (Figure 5.9,
bottom; P ≤ 0.001) detected. Univariate post hoc analyses revealed a significant
increase in DOMS at 24 hours post-exercise following BFR-C and BFR-I (P ≤ 0.01)
relative to baseline. In addition, DOMS was higher for BFR-C and BFR-I in
comparison with HL (P ≤ 0.05) only. At 48 hours post-exercise, DOMS remained
elevated for BFR-C (P ≤ 0.05) and BFR-I (P ≤ 0.001) in comparison with baseline. In
addition, the magnitude of the increase in DOMS remained significant for BFR-I in
comparison with HL and LL (P ≤ 0.01). There were no other differences between trials
or time-points.

162
Figure 5.9 Perceptual responses following all four trials.
* indicates significant difference compared with Baseline (P ≤ 0.05).
a indicates significant difference compared with HL (P ≤ 0.05).
b indicates significant difference to LL (P ≤ 0.01).
c indicates significant difference to BFR-C (P ≤ 0.01).

163
5.4 Discussion
The present study examined the acute haemodynamic responses to BFR-RE in
comparison with more traditional resistance exercise techniques, while also examining
these responses under different methods of BFR application (continuous low-pressure
BFR versus intermittent high-pressure BFR). The major findings showed HR, blood
pressures, Q̇ , and RPP to be significantly greater during HL and BFR-I, in comparison
with LL, while the magnitude of the haemodynamic responses during BFR-C most
often resided between HL/BFR-I and LL. Following exercise there was a rapid return to
baseline of all haemodynamic variables independent of trial, which suggests that there
is no persistent effect of BFR on autonomic control of haemodynamics. These results
support the authors’ hypothesis, and suggest that in order to limit the haemodynamic
stress during light-load (20% 1-RM) exercise in combination with BFR, continuous
low-pressure application is preferential to intermittent high-pressure application.
The present study directly compared the haemodynamic responses to BFR-RE with
both HLRE and LLRE. It is of particular interest to compare against HLRE because
light-load BFR-RE has been suggested as an alternative to HLRE when used
chronically over a period of training to develop muscle strength and increase muscle
mass (Clark et al., 2010, Karabulut et al., 2011a, Laurentino et al., 2012, Takarada et
al., 2000c, Thiebaud et al., 2013a). During HLRE the magnitude of the increase in
blood pressure is substantial (Fleck, 1992, MacDougall et al., 1985). MAP would be
expected to rise to ~200 mmHg during a single set of elbow flexion exercise at 95% 1-
RM (MacDougall et al., 1985), and to even greater levels during unilateral or bilateral
leg press exercise (≥ 250 mmHg) (MacDougall et al., 1985). Investigations of BFR-RE
have also reported significant elevations in blood pressure when compared with resting
values (Downs et al., 2014, Renzi et al., 2010, Takano et al., 2005). However, rarely

164
have comparisons been made with responses to HLRE in the same participants.
Therefore, a novel element of the present study was that the blood pressure responses
during HL, and also during BFR-I, were elevated to a larger extent compared with LL.
These are similar to previous observations where HR and blood pressure were elevated
with BFR-RE when compared with non-BFR LLRE (Downs et al., 2014, Takano et al.,
2005). However, with continuous low-pressure restriction in the present study (BFR-C)
these elevations in blood pressure were attenuated (Figure 5.6-5.8). In contrast, Downs
et al., (2014) showed both systolic BP and diastolic BP to be higher during lower body
resistance exercise with continuous BFR compared with both LLRE and, interestingly,
HLRE. However, it is important to note that these participants exercised to failure,
rather than the somewhat standard sets/reps regimen conducted in the present study.
Although Q̇ increased during exercise in all trials, it was greatest during HL, and was
not different between LL, BFR-I and BFR-C. These findings are consistent with
previous observations where Q̇ increased to a similar extent with both BFR-RE and
LLRE (Takano et al., 2005). In contrast, Downs et al., (2014) showed the increase in Q̇
be greatest with HLRE as well as LLRE when compared with BFR-RE, while only low-
pressure BFR exercise increased Q̇ and not high-pressure BFR-RE (Downs et al., 2014).
Again, these contrasting results are likely explained by the exercise being to fatigue
(Downs et al., 2014) rather than a less fatiguing BFR training regimen (Takano et al.,
2005).
While SV is expected to decline during BFR-RE due to the reduction in venous return
(Ozaki et al., 2010, Renzi et al., 2010, Takano et al., 2005), it is interesting that no
change was observed in SV during either BFR-C or BFR-I. The absence of a reduction
in SV does not appear to be related to the applied pressure given the similar response in

165
both BFR-C and BFR-I, and so may be related to the use of a single limb and small
muscle group, whereby no change in SV was also evident for both HL and LL trials.
Therefore, under these conditions the increase in Q̇ during BFR-RE appears largely
driven by the increase in HR and TPR, but not SV.
Larger increases in RPE occur with BFR-RE in comparison with LLRE without BFR,
as long as the exercise protocol is not performed to failure (Hollander et al., 2010,
Loenneke et al., 2010a, Wernbom et al., 2006, Wernbom et al., 2009, Fitschen et al.,
2013). These results are in agreement with the current study. Furthermore, it was
demonstrated that RPE was higher for BFR-I in comparison with BFR-C, suggesting
that despite the intermittent application of pressure (which is suggested to be more
tolerable than continuous application of pressure) if the pressure is too high then this
may limit its use in some populations. In addition to the rise in RPE immediately
following the exercise trial, DOMS was significantly increased for 48 hours post-
exercise for BFR-C and BFR-I. In agreement with this, both Umbel et al., (2009) and
Wernbom et al., (2006a, 2009) reported similar time-course manifestations and
significant elevations of DOMS following knee extension exercise to muscular failure
with BFR. Unexpectedly, we did not observe an increase in DOMS following the HL
trial. Perhaps a limitation to the current HL trial was that not all participants were able
to complete the full exercise protocol (4 sets of 8 repetitions) due to the heavy load
(80% 1-RM) in conjunction with the repetition timing. It might be expected that if more
repetitions were prescribed during the HL trial that the DOMS responses would have
increased to levels similar to those reported previously (Chen et al., 2010). In addition,
we acknowledge that one of the main limitations of the DOMS data is that although
participants completed the trials in a randomized, counterbalanced order, we cannot rule
out the repeated bout effect that is often associated with DOMS (McHugh, 2003). That

166
is, prior resistance exercise trials can protect against high levels of DOMS occurring in
subsequent resistance exercise bouts. Nevertheless, results from the current study
suggest that a high volume of work and time under tension in combination with the
BFR stimulus may be one possible explanation for the increase in DOMS.
While there is no standard method for the application of BFR during exercise, in the
present study we sought to compare the acute haemodynamic responses between
continuous low-pressure and intermittent high-pressure BFR-RE. Our data demonstrate
that a high-pressure restriction applied during exercise only (BFR-I, 130% systolic BP;
151 ± 4 mmHg) generally produced a greater elevation in a number of haemodynamic
variables and perceptual responses in comparison with a low-pressure restriction
applied continuously throughout a whole bout of exercise (BFR-C, 80% systolic BP; 91
± 4 mmHg). Of note, HR and blood pressures were typically much higher during BFR-I
in comparison with BFR-C. This indicates that a high-pressure restriction combined
with relatively wide cuffs (i.e. BFR-I) increases myocardial work in comparison with a
low-pressure restriction applied continuously without release (i.e. BFR-C). This low-
pressure continuous restriction eliminates the likelihood of complete arterial occlusion
and, therefore, any possibility of thrombus formation (Rossow et al., 2012, Loenneke et
al., 2014b). Nerve conduction velocity is likely unaffected by low-pressure BFR-RE
(Mittal et al., 2008), and while tissue oxygen saturation is reduced (Downs et al., 2014),
exercise is often reported to be more tolerable (Hollander et al., 2010, Loenneke et al.,
2010a, Vieira et al., 2014). Taken together with previous studies, in comparison with
high-pressure BFR-RE, a low-pressure continuous restriction seems preferential when
using relatively wide cuffs like those of the present study given the reduced
haemodynamic stress and RPE, but should not be expected to provide any lesser

167
beneficial adaptations to muscle strength and mass when undertaken across a training
period (Wernbom et al., 2008).
There are several limitations to the present study that must not be overlooked when
interpreting the results. The present study examined healthy young participants and so
limits the extrapolation to other populations. However, recently using a similar exercise
protocol, haemodynamics were not different for BFR-RE between both young (30 ± 3
yrs) and older (66 ± 7 yrs) healthy and recreationally active participants (Vieira et al.,
2012). Therefore, it seems likely that BFR-RE may indeed be particularly useful to gain
muscle strength and mass in populations that are often contraindicated to HLRE.
Secondly, the present exercise protocol reflects acute haemodynamic responses to
exercise with a small muscle mass. While these results may not directly apply to
exercise using multiple/larger muscle groups, our findings are similar to previous
experiments in young healthy participants during lower body resistance exercise
(Takano et al., 2005) and walking (Renzi et al., 2010). Similarly, the upper body
exercise in the present study was undertaken in an upright standing position and so may
not extrapolate to other upper body exercises that utilise different postures such as the
supine bench press.

168
5.5 Conclusion
In conclusion, the present study showed that light-load resistance exercise in
combination with a continuous BFR (80% systolic BP; 91 ± 2 mmHg) demonstrates a
limited rise in HR, blood pressure, Q̇ , RPP, and RPE to levels between those observed
for HLRE and LLRE. However, when a higher BFR pressure was applied intermittently
during exercise only, HR and blood pressures were similar to HLRE and greater than
LLRE. Therefore, continuous low-pressure BFR-RE appears a preferential BFR training
method to target gains in strength and muscle mass in healthy young populations, and
perhaps more importantly in special populations such as the elderly and a variety of
clinical conditions where gains in muscle mass and strength are beneficial.

169
CHAPTER SIX:
Corticomotor adaptations to blood flow restriction
training and de-training

170
6.1 Introduction
The neurophysiological adaptations that underpin the increase in muscle strength
following light-load resistance training (LLRT) combined with blood flow restriction
(BFR) remain unknown. Despite this, there is some good evidence to show that under
acute ischemic conditions, either with exercise (Yasuda et al., 2012a, Yasuda et al.,
2006, Moore et al., 2004, Takarada et al., 2000c) or without (Ridding and Rothwell,
1995, Brasil-Neto et al., 1993a, Brasil-Neto et al., 1993b, Vallence et al., 2012,
Ziemann et al., 1998a), indices of the central nervous system are modulated at multiple
levels of the neuroaxis including at a cortical, spinal, and motor unit level (Griffin and
Cafarelli, 2005, Carroll et al., 2011). Results from chapter four (pages 115-141)
revealed that when low-pressure continuous BFR was combined with light-load elbow
flexion exercise, a rapid (within 5 min) and long-lasting (up to 60 min) increase in
corticomotor excitability was observed. This finding supports previous investigations of
use-dependent plasticity following motor skill learning tasks (Jensen et al., 2005, Leung
et al., 2015) and traditional heavy-load resistance exercise (Carroll et al., 2008, Sacco et
al., 1997, Selvanayagam et al., 2011, Leung et al., 2015), as well as ischemic nerve
deafferentation (Ridding and Rothwell, 1995, Brasil-Neto et al., 1993b, Brasil-Neto et
al., 1993a, Vallence et al., 2012, Ziemann et al., 1998a). This evidence is promising
with regard to the acute modulation of corticomotor plasticity following BFR resistance
exercise (BFR-RE); however, currently it is unclear what effect BFR has on
corticomotor plasticity following short- and long-term resistance training programmes
(BFR-RT).
With the use of transcranial magnetic stimulation (TMS), longer lasting adaptations in
corticomotor plasticity identified at the level of the primary motor cortex (M1) have
been reported following short- and long-term heavy-load resistance training (HLRT)

171
programmes (Hortobágyi et al., 2011, Latella et al., 2012, Kidgell et al., 2010). As an
example, Hortobágyi et al., (2011) detected a 49.9% increase in muscle strength
following eight weeks of HLRT, in combination with a 63.9% increase in corticomotor
excitability. Furthermore, following eight weeks of leg press training at 70-88.5% 1-
RM, Latella et al., (2012) reported a 33.8% increase in strength as well as a reduction in
corticomotor inhibition. Currently, no study has used TMS to investigate adaptations in
corticomotor plasticity following BFR-RT. Therefore, the potential underlying
mechanisms by which BFR-RT increases muscle force production and overall
functional capacity remain to be elucidated.
Investigation of corticomotor responses following BFR-RT may provide a greater
understanding of the underlying mechanisms responsible for the increase in muscle
strength following both short- and long-term BFR-RT programmes. Therefore, the aim
of this study was four fold; (i) to investigate the acute corticomotor responses to an
acute bout of BFR-RE of the lower-body; (ii) to investigate the time-course training and
de-training related corticomotor adaptations to a full-body BFR-RT programme; (iii) to
measure the time-course adaptations in muscle strength and mass following a full-body
BFR-RT and de-training programme; and (iv) to compare these results to more
traditional resistance training programmes such as HLRT and LLRT. It was
hypothesised that the increase in muscle strength and mass would be greatest for HLRT
and BFR-RT, and that these adaptations would be maintained above baseline levels
following a four week de-training period. It was expected that BFR-RT will modulate
indices of the corticomotor pathway similar to HLRT.

172
6.2 Methods
The final study within this thesis contains a large number of variables that were
measured over a 12 week training and de-training programme. As such, this study was
divided into two parts (chapter six and seven) to provide a more clear presentation of
the description of the study design, methods, and results, in order to improve the
understanding and interpretation for the reader. Much of the technical methodology for
the measurements employed within this thesis is described in chapter three (page 96)
and will be referred to accordingly. Specifically, chapter six focuses on neuromuscular,
maximal dynamic strength, and muscle mass adaptations, while chapter seven focuses
on haemodynamic and perceptual adaptations to training and de-training.
6.2.1 Participants
Thirty nine healthy participants (27 males and 12 females, 23 ± 1 years) volunteered to
take part in a resistance training and de-training study, and provided written informed
consent to the experimental procedures prior to participation. All participants in this
study were recruited in accordance with the general methods employed in chapter three;
section 3.1 (page 97). Study sample size was determined by undertaking a power
analysis (G*Power v 3.1.9.2). Sample size for the current chapter was based on
previous studies investigating muscular adaptations following knee extension exercise
with BFR (Takarada et al., 2002, Kacin and Strazar, 2011, Fujita et al., 2008a,
Karabulut et al., 2010b), with power set to ≥ 0.80 to detect significant increases in
muscle strength and mass at P ≤ 0.05.

173
6.2.2 Anthropometrics
Anthropometric measurements were taken according to procedures described in the
general methods. For a more detailed description of the anthropometrics procedures
employed, refer to chapter three, and section 3.2 (page 98).
Figure 6.1 provides an overview of the experimental procedure for study three. The
total duration of the experimental study was 12 weeks. Prior to beginning the study,
participants were familiarised with all testing and exercising procedures and completed
(i) anthropometric measurements, (ii) blood pressure assessment and BFR
familiarisation, including measurement of limb occlusion pressure (LOP), (iii)
familiarisation with all neuromuscular and haemodynamic testing procedures, and (iv)
familiarisation with all resistance exercises. In addition, participants were informed of
the requirements of the resistance training programme which involved three lower-body
and three upper-body exercises.
Approximately one week after familiarisation, participants reported to the laboratory on
two separate occasions, on non-consecutive days, and undertook baseline testing prior
to beginning training. During the first testing session, body composition was measured
using Dual X-ray Absorptiometry (DXA), with ultrasound used to measure muscle
thickness (MTH) at seven sites. Following this, and on the same day, maximal dynamic
strength (1-RM) was measured for six resistance exercises, including knee extension
(KE) exercise as the main outcome measure for strength. After this initial evaluation,
participants were matched for 1-RM KE strength and then randomly allocated to one of
three resistance training groups (n = 32) or a control group (CON; n = 7). Participants

174
allocated to the resistance training were then further divided into one of three resistance
training groups which were as follows; heavy-load resistance training (HL-T; n = 11),
light-load resistance training (LL-T; n = 10), or light-load resistance training in
combination with continuous BFR (BFR-C; n = 11). For full details of the resistance
training undertaken by each group, see section 6.2.4.
Randomization was essential to be conducted prior to the second testing session,
whereby participants completed neuromuscular testing (section 6.2.5) at rest prior to
exercise. Following this, participants were moved to the KE machine (Nautilus Nitro,
Vancouver, WA) whereby haemodynamic responses (see chapter seven, section 7.2.6,
page 229) were taken at rest prior to exercise in a seated position, and also during the
final repetitions of set four of the exercise bout (peak-exercise). Therefore,
measurements were taken pre-exercise at rest and at peak-exercise to measure the acute
haemodynamic responses, as well any chronic training related adaptations as measured
over the training weeks. As there were no differences observed during the post-exercise
recovery period in comparison with rest for all haemodynamic variables as measured in
chapter four, haemodynamic responses were not collected in post-exercise recovery
period in the current study. Following KE, and immediately prior to neuromuscular
testing, participants provided their perceptual responses (see chapter seven, section
7.2.7, page 230) to the KE exercise, and then began the neuromuscular testing again at
5, 30, and 60 minutes post-exercise. Figure 6.2 shows an example of the acute
neuromuscular, haemodynamic, and perceptual responses that were taken within a
single testing session.

175
Figure 6.1 Overview of the entire timeline of testing across 12 weeks for study three.
Familiarisation occurred approximately one week prior to beginning the intervention. On non-
consecutive days participants completed muscle mass and maximal strength testing (grey),
followed by neuromuscular, haemodynamic, and perceptual testing (white) for the knee
extension exercise (see also Figure 6.2). Both testing sessions were completed separately after
four and eight weeks of resistance training (HL-T, LL-T, and BFR-C), or no training (CON).
Participants were then instructed not to complete any resistance training for four weeks before
returning to the laboratory for the final testing sessions at week 12.

176
Participants assigned to the resistance training groups were required to undertake 10
supervised training sessions for four weeks. The resistance training loads for all
exercises were adjusted to the participants’ new 1-RM strength, before completing
another 10 training sessions for four weeks. Thereafter, participants underwent a four
week de-training period without any resistance training at all. All testing sessions were
completed at the mid-point (week 4), end of training (week 8), and following the de-
training period (week 12). Measurement of physical activity levels, type of activities
performed, and nutritional intake was not monitored throughout the duration of the
study period. However, all participants included in the study did not complete resistance
training for the three months prior, and at the completion of the training programme at
week 8, participants were requested not to perform any form of resistance training
during the four week de-training period. Participants assigned to the CON group
completed no resistance training, but participated in all testing sessions and were
instructed to continue their current activities of daily living for the study period. All
participants were instructed to avoid caffeine, medications, and exercise on the day of
each testing session.

177
Figure 6.2 Overview of the acute neuromuscular, haemodynamic, and perceptual testing measurements. Prior to exercise all neuromuscular measurements were
taken on the quadriceps. Participants were then transferred to the Knee extension (KE) machine where haemodynamic measurements were taken pre-exercise at rest.
Participants completed four sets of KE, and haemodynamic measurements were taken during the final repetitions of set 4 (peak-exercise). Perceptual responses were
measured 5 min post-exercise immediately prior to neuromuscular testing, which occurred at 5 min, 30 min, and 60 min post-exercise.
177

178
6.2.4 Resistance training programme
Participants in the resistance training groups performed 20 resistance training sessions
using training programs specifically designed for each group (see Appendix ii). The
primary investigator was present to supervise all resistance training sessions throughout
the experiment, and was assisted by two students of the department. Training each week
was undertaken on three non-consecutive days (i.e. Monday, Wednesday, and Friday).
All resistance training sessions comprised three lower- and three upper-body exercises.
Prior to each session, participants began a standardised warm up consisting of 5 minutes
on a Monark cycle ergometer. Subsequently, participants began training and completed
the exercises in the following order; knee extension (KE), barbell back squat (SQ), calf
raise (CR) on a 45º leg press, barbell bench press (BBP), seated row (SR), and barbell
biceps curl (BC). The exercises were chosen based on their common inclusion in
resistance training programmes for the development of muscle strength and mass
(Baechle and Earle, 2008). The reader is directed to Figures 6.5 and 6.6 for examples of
the resistance exercises. While the load and repetitions performed for all groups were
different (see below; sections 6.2.4.1-6.2.4.3), there were some similarities between
training programmes that can be explained herein. For all groups, four sets were
performed for KE as an equivalent to the standard four sets performed for BFR-RT
(Fahs et al., 2012). Due to time limitations, only three sets were performed for all other
exercises, although these still meet the recommendations for traditional resistance
training and BFR-RT to enhance muscle strength and mass. Between the three lower-
and three upper-body exercises there was a 5 minute recovery period. All repetitions for
all resistance exercises for all groups were monitored by a metronome with a repetition
timing of 2 seconds for the concentric phase and 2 seconds for the eccentric phase. In
total, the duration of each training session took approximately 45 minutes. While the
HL-T, LL-T, and BFR-C training programmes utilized in the current study were

179
different, these represent the typical and proven protocols for each type of exercise for
the development of muscle strength and mass, which was the practically relevant
rationale for their comparison.
6.2.4.1 Heavy-load resistance training
Participants in the HL-T group were required to exercise at 70% 1-RM. For KE,
participants performed four sets of 8-10 repetitions, separated by 1 minute rest between
sets. Following this, participants completed the additional five exercises, but were only
required to complete three sets of 8-10 repetitions. There was a 1 minute recovery
period between all exercises and sets.
6.2.4.2 Light-load resistance training
Participants in the LL-T group were required to exercise at 20% 1-RM. For KE,
participants performed a total of 30 repetitions in the first set, followed by three sets of
15 repetitions. The rest period between sets was 30 seconds. Following this, participants
completed the additional five exercises, but were only required to complete three sets of
15 repetitions. This repetition protocol has also been used previously in the BFR
literature (Sakuraba and Ishikawa, 2009, Kim et al., 2009, Kim et al., 2012b, Karabulut
et al., 2010a, Karabulut et al., 2011a). There was a 30 second rest period between sets,
and a 1 minute recovery period between all exercises and sets.
6.2.4.3 Blood flow restriction resistance training
Participants were required to perform the same resistance training programme as
described above in section 6.2.4.2. However, during exercise participants were required

180
to exercise according to the BFR protocol as described in the general methods in
chapter three, and section 3.3 (page 98). In addition, and specific to this study, based on
results from chapter four and chapter five, it was decided that only the low-pressure
continuous BFR protocol would be employed for the current study chapter. Participants
in the BFR-C group were familiarised with the technique prior to beginning the study.
There has been some recent evidence to suggest that setting the final cuff pressure
should be determined according to an individual’s limb circumference and width of
cuff, whilst basing pressures off participants’ systolic blood pressure may not account
for any variance in the maximal arterial occlusion pressure (Loenneke et al., 2011c,
Crenshaw et al., 1988). Therefore, the final cuff pressures used in this study were set
according to each individuals limb occlusion pressure (LOP) as determined by digital
plethysmography, which has been shown to be accurate and reliable in determining
cessation of limb blood flow in comparison with Doppler (McEwen et al., 2002,
Younger et al., 2004). To determine LOP, participants were required to remain seated in
an upright position where the lead investigator applied the cuffs firmly to the most
proximal portion of both thighs and arms using the same cuffs as previously described
in the general methods. Thereafter, a plethysmograph (Pulse Sensor, Zimmer ATS
3000) was then applied to the participants’ second toe or finger before beginning LOP
measurement (Figure 6.3). Using the LOP setting (A.T.S. 3000, Zimmer Inc., OH,
USA) the cuffs automatically inflated to produce a continuous rise in pressure until the
plethysmograph could no longer receive a pulse signal and LOP was reached. This
process was conducted at least twice on each limb for the lower- and upper-body in
order to ensure a consistent LOP reading. If the measured LOP were less than 20
mmHg different, an average of the two measurements was taken. However, if the
measurements were more than 20 mmHg apart on each limb, a third test would be
conducted and an average of all three tests would be taken. The final exercise pressure

181
used for the upper- and lower-body was equal to 60% LOP, which has been used
previously in the BFR literature (Loenneke et al., 2015, Neto et al., 2014a).
Figure 6.3 The Zimmer Automatic Tourniquet System (A.T.S) 3000 with Limb occlusion
pressure technology. Image taken from http://www.zimmer.com.
With regard to the LOP measurement for this study, LOP measurements were taken on
two occasions, once at baseline, and again at week 5 prior to the second half of the
training program, in order to account for any changes in muscle mass. If LOP was
different for a participant, their final exercising pressure was set according to their new
LOP in the second four week training period. However, there were no statistical
differences between final cuff pressures for both lower- and upper-body between the
first four weeks and final four weeks of training (Table 6.1).

182
Table 6.1 Limb occlusion pressure and subsequent exercise pressures.
LOPaverage 60% LOP
Lower-body
Week 0 180 ± 7 107 ± 5
Week 5 181 ± 8 109 ± 5
Upper-body
Week 0 133 ± 3 80 ± 2
Week 5 136 ± 5 81 ± 3
LOP, limb occlusion pressure; 60% LOP, the final cuff pressure used for participants in the
blood flow restriction resistance training trial. Data presented as Mean ± SEM.
Prior to beginning each training session, participants in the BFR group were fitted with
cuffs to the most proximal portion of each thigh (Figure 3.2, left, page 100) in order to
perform all three lower-body resistance exercises. The final exercising BFR pressure
was set immediately prior to KE and was maintained continuously throughout all three
lower-body resistance exercises (approximately 16 minutes) before the cuffs were
deflated. Participants were then given a 5 minute recovery time, and fitted with cuffs to
the most proximal portion of their upper arms (Figure 3.2, right, page 100). The final
exercising BFR pressure was set immediately prior to BBP and was maintained
continuously throughout all three upper-body resistance exercises (approximately 14
minutes) before cuff deflation.
6.2.5 Neuromuscular measurements
Given that the main outcome exercise for this study was the KE, all acute and chronic
neuromuscular testing was conducted pre- and post- KE exercise (Figure 6.2). It should
be noted that all exercise parameters (loads lifted, and final restriction pressure for the
BFR-C group) during testing remained the same throughout the duration of the study
(i.e. the loads and BFR pressure that were used in the baseline testing session, were the
same at weeks 4, 8, and 12). Surface EMG, MEP amplitude, SICI, and M-waves were

183
taken prior to performing KE (pre-exercise), and then at three time points post-exercise
(5 min, 30 min, and 60 min) to measure the acute response in corticomotor function. In
addition, stimulus response curves were collected prior to performing KE (pre-
exercise), and taken to measure any chronic training related corticomotor adaptations
over the training duration (i.e. baseline, 4, 8, and 12).
Figure 6.4 Visual representation of the experimental set up. a represents the placement of the
circular coil, held tangential to the skull in an anterior-posterior orientation, so that the current
activated the left M1 (right-side muscles). In addition, the participant is wearing the fitted cap
with markings of 1 cm distance in both anterior-posterior and medial-lateral directions; b
represents the paired-pulse magstim; c represents visual feedback on the computer monitor; and
d represents the isokinetic dynamometer.
6.2.5.1 Electromyography and transcranial magnetic stimulation
Surface EMG and TMS testing were collected according to the general methods
described in chapter three, and section 3.5 (page 107). In addition, specifically to this
study, surface EMG was recorded using Ag-AgCl electrodes from the rectus femoris
a
b
c
d

184
muscle of the participants’ dominant leg (Chapman et al., 1987). Two electrodes were
placed over the muscle belly of the rectus femoris located at a distance of 50% between
the ASIS and the patella, and one reference electrode was positioned on the
participants’ patella. All cables were fastened with tape to prevent movement artefact.
Similar protocols for measuring surface EMG of the rectus femoris have been used
previously (Goodwill et al., 2012, Latella et al., 2012, Weier et al., 2012).
For TMS, a 70 mm double cone coil was used in this study. The handle of the TMS coil
was positioned over the “optimal” site (the location on the M1 that evokes the
maximum MEP amplitude to the rectus femoris), and oriented so that the axis of the
intersection between the two loops was oriented to induce a posterior-anterior current
flow across the motor strip for activating the dominant M1 and quadriceps muscle
(Figure 6.4). All TMS measures were taken during a weak contraction, where
participants were instructed to perform a 10% MVIC, as indicated by a visual line
representing knee extension force on a computer monitor positioned approximately 1.5
m away at eye level connected to an isokinetic dynamometer (Biodex system 4 Pro,
Biodex Medical Systems, Shirley, TX, USA; Figure 6.4, c). The participants were
instructed to maintain the response cursor at the level of the stationary cursor prior to
each single- and paired-TMS pulse. Root mean square (rms) of the rectus femoris
muscle EMG was obtained prior to each TMS stimulus to ensure that there were no
changes in pre-stimulus rmsEMG pre-KE exercise and post-exercise, which may have
altered MEP amplitude.

185
6.2.5.2 Active motor threshold
Active motor threshold (AMT) was defined as the stimulus intensity at which an MEP
could be could be obtained with at least 3 out of 5 stimuli with a peak-to-valley
amplitude greater than 200 µV. Each of the five stimuli were delivered during a
controlled, low level voluntary activation of the rectus femoris muscle at ≤ 10 ± 3% of
MVIC rmsEMG (Goodwill et al., 2012, Weier et al., 2012). Each stimulus was
delivered in random intervals every five to 12 seconds to avoid stimulus anticipation,
and 30 seconds rest was provided between each set of stimuli to reduce the possibility
of muscular fatigue.
6.2.5.3 Motor evoked potentials and short-interval intracortical inhibition
All single- and paired-pulse TMS measurements were taken according to procedures
described in the general methods. For a more detailed description of the general
methods employed, refer to chapter three, and sections 3.5.4 (page 108).
6.2.5.4 Stimulus response curves
The stimulus intensities used to establish the TMS recruitment curves were determined
for each individual according to the AMT prior beginning to the resistance training
intervention. At each stimulus intensity, five stimuli were applied over the contralateral
M1, with the percentage of stimulator output delivered in a pseudo-randomized fashion.
Each set of stimuli were given at a stimulus intensity according to the participants
AMT. The intensities used were 90, 110, 130, 150, and 170% of AMT or until no
further increase in MEP amplitude was observed (MEPMAX). Each stimulus was
delivered in random intervals every five to 12 sec to avoid stimulus anticipation, and 60

186
sec rest was provided between changes in stimulus intensity to reduce the possibility of
muscle fatigue.
6.2.5.5 Maximal muscle compound action potential
The measurement of the maximal muscle compound action potential (MMAX) was
completed according to the general methods in chapter three, and section 3.5.5 (page
109). In addition, specifically to this study, MMAX was obtained from the participants’
dominant rectus femoris by supramaximal electrical stimulation of the femoral nerve
under resting conditions in a supine position at all time-points. The site of stimulation
that produced the largest MMAX was located by positioning Ag-AgCl electrodes in the
femoral triangle lateral to the femoral artery, 3-5 cm below the inguinal ligament
(Goodwill et al., 2012, Latella et al., 2012, Weier et al., 2012).
6.2.6 Measurement of muscle strength and mass
The measurement of maximal dynamic muscle strength (1-RM) and muscle mass was
completed according to the general methods in chapter three, and sections 3.4.1 (page
101) and section 3.4.2 (page 102), respectively.
6.2.6.1 Maximal strength testing
Participants in all trials performed 1-RM testing for three lower- and three upper-body
resistance exercises which included; KE (see Figure 6.5, left; Nautilus Nitro® Plus Leg
Extension, Vancouver, WA, USA), SQ (Figure 6.5, centre), CR (Figure 6.5, right), BBP
(Figure 6.6, left), SR (Figure 6.6, centre), and BC (Figure 6.6, right). The 1-RM testing
for these resistance exercises has been previously shown to be highly reliable in healthy

187
participants (Seo et al., 2012). All exercises requiring free-weight lifting with barbells
(e.g. SQ, BBP, and BC) were conducted with a plate-loaded Olympic barbell (Eleiko,
Sweden). Please refer to chapter three, section 3.4.1 (page 101) for a detailed
description of the methods employed for 1-RM testing. To determine whether a 1-RM
lift was successful or not the following requirements were met by participants;
i. Knee extension: full extension at the knee joint.
ii. Squat: squat to 90º parallel as determined during familiarisation.
iii. Calf raise: tape measure to measure full plantar flexion.
iv. Barbell bench press: bar lowered to chest, then to full elbow extension without
assistance.
v. Seated row: using a V-bar, participants required to remain upright in seated
position, flex the elbows until the V-bar touched their mid-sternum.
vi. Barbell biceps curl: standing against wall, participants were required to maintain
head, back, and gluteal contact while performing full flexion of the elbow joint.

188
Figure 6.5 Participant performing strength testing for the lower-body. Images displayed on top represent starting position, while images on the bottom are the
finishing position through a full range of motion. Knee extension depicted on left, squat depicted in centre, calf raise depicted on right.
188

189
Figure 6.6 Participant performing strength testing for the upper-body. Images displayed on top represent starting position, while images on the bottom are the
finishing position through a full range of motion. Barbell bench press depicted on left, seated row depicted in centre, biceps curl depicted on right.
189

190
6.2.6.2 Dual energy X-ray absorptiometry
Body composition measurements were taken using Dual energy X-ray absorptiometry
(DXA) and collected according to procedures described in the general methods. For a
more detailed description of the protocol used for DXA measurements, refer to chapter
three, and section 3.4.2.1 (page 102).
6.2.6.3 Ultrasound
Measurement of muscle thickness (MTH) was taken using Ultrasound and collected
according to the procedures described in the general methods. For a more detailed
description of the protocol used for MTH measurements, refer to chapter three, and
section 3.4.2.2 (page 103). In addition, specific to this study, MTH measurements were
obtained 48-72 hours following the final resistance training session of week four and
week eight in order to ensure that muscle swelling did not obscure results (Fujita et al.,
2008b, Abe et al., 2005a, Farup et al., 2015).
6.2.7 Data analyses
The data analyses used in the current study for rmsEMG, MEP amplitude, MMAX, and
SICI were identical to those discussed in chapter four, and section 4.2.8 (page 128). In
addition, specific to this study, rmsEMG activity was determined for the rectus femoris
100 ms prior to each TMS stimulus for each group at each time-point. Any pre-stimulus
rmsEMG that exceeded 10% of maximal rmsEMG was discarded and the trial repeated.
The peak-to-valley amplitude of MEPs evoked as a result of stimulation was measured
in the rectus femoris muscle contralateral to the cortex being stimulated in the period
10-50 ms after stimulation. MEP amplitude were analysed using LabChart software (8,

191
with a cursor, providing peak-to-valley values in μV and were then normalized to
MMAX. Average MEP amplitude was obtained separately for single- and paired-pulse
TMS for each stimulation block (20 trials for each time point). SICI was calculated
using the following equation: (1 – PP/SP) x 100. This calculation, adapted from
Lackmy et al., (2010), has a direct relationship with SICI (unlike the traditional method
for calculating SICI ratio). For example, a decrease in inhibition following the
intervention would be depicted by a decrease in the numerical value.
All data for measured variables were found to be normally distributed as assessed with
a Shapiro-Wilks test (P ≤ 0.05). Repeated measures ANOVA was used to measure main
effects for GROUP (HL-T, LL-T, BFR-C, and CON), TIME (pre-exercise, 5 min post,
30 min post, and 60 min post), and WEEK (baseline, week 4, week 8, and week 12). If
any interactions occurred, Tukey post-hoc was used to determine differences for each
dependent variable. The repeated measures ANOVA were performed using NCSS
statistical software (version 2007). Effect sizes (ES) were determined for muscle
strength and mass measurements, and calculated as [(Post-training mean – Pre-training
mean)/Pre-training SD] with scores for untrained individuals set as trivial (< 0.50),
small (0.50-1.25), moderate (1.25-1.9), and large (> 2) as previously suggested (Rhea,
2004). The level of significance was set at P ≤ 0.05 and all data is presented as mean ±
standard error of the mean (SEM) unless stated otherwise.

192
6.3 Results
6.3.1 Participant characteristics
Table 6.2 shows the mean ± SEM for the baseline anthropometric variables for each
group. At baseline, no significant differences were observed between groups for age,
height, body mass, and body mass index.
Table 6.2 Anthropometric characteristics as measured at baseline.
HL-T
(n = 11)
LL-T
(n = 10)
BFR-C
(n = 11)
CON
(n = 7)
Gender (M, F) 7, 4 7, 3 8, 3 5, 2
Age (years) 23 ± 1 23 ± 1 23 ± 1 24 ± 1
Height (cm) 171.5 ± 2.8 177.0 ± 4.4 175.0 ± 3.9 183.2 ± 3.0
Body mass (kg) 71.1 ± 3.8 74.5 ± 6.7 73.0 ± 4.9 77.5 ± 4.8
BMI (kg/m2
) 24 ± 1 21 ± 2 24 ± 1 20 ± 2
BMI, body mass index; BFR-C, blood flow restriction with continuous application of pressure;
CON, control; HL-T, heavy-load resistance training; LL-T, light-load resistance training.
6.3.2 Maximal strength
6.3.2.1 Lower-body strength
Figure 6.7 shows the normalized lower-body 1-RM changes across the duration of the
study period for each group. There were some significant differences in absolute lower-
body 1-RM between groups at baseline (P ≤ 0.05). There were significant GROUP x
WEEK interactions detected for absolute and normalized KE 1-RM (P ≤ 0.001) and SQ
1-RM (P ≤ 0.001). In addition, for CON, all lower-body 1-RM exercises did not change
at all other time-points in comparison with baseline (all P ≥ 0.05).

193
For KE 1-RM (see Figure 6.7), a significant GROUP x WEEK interaction was detected
(P ≤ 0.001). At week 4, KE 1-RM increased relative to baseline for HL-T (15.0%;
small) and BFR-C (13.9%; trivial). At week 8, KE 1-RM remained elevated in
comparison with baseline for HL-T (25.8%; small) and BFR-C (20.1%; trivial), and was
also higher for LL-T (13.4%; trivial). Following the de-training period, KE 1-RM
remained significantly elevated in comparison with baseline at week 12 for HL-T
(21.0%; small) and BFR-C (14.4%; trivial) only. The increase in KE 1-RM observed
was similar between training groups (HL-T, LL-T, and BFR-C) at almost all time-
points, while all groups appeared to be greater than CON at some time-points.
For SQ 1-RM (see Figure 6.7), a significant GROUP x WEEK interaction was detected
(P ≤ 0.001). At week 4, SQ 1-RM increased relative to baseline for LL-T only (14.0%;
trivial). At week 8, SQ 1-RM remained elevated in comparison with baseline for LL-T
(24.1%; small), and was also higher for HL-T (20.6%; small). Following the de-training
period, SQ 1-RM remained elevated at week 12 for HL-T (12.4%; trivial) and LL-T
(25.2%; small) only. There were some significant differences between groups in
absolute SQ 1-RM at all time-points, but the normalized increase in SQ 1-RM appeared
greatest for LL-T in comparison with all groups at most time-points, with no other
differences between groups.
For CR 1-RM (see Figure 6.7), a significant main effect for WEEK (P ≤ 0.001) was
detected, while there was a trend for GROUP x WEEK interaction (P = 0.076). When
the data was grouped, CR 1-RM was increased at all time-points in comparison with
baseline.

194
6.3.2.2 Upper-body strength
Figure 6.7 shows the normalized upper-body 1-RM changes across the duration of the
study period for each group. There were significant differences in absolute upper-body
1-RM between groups at baseline (P ≤ 0.05). There were significant GROUP x WEEK
interactions detected for absolute and normalized BBP 1-RM (P ≤ 0.001) and SR 1-RM
(P ≤ 0.001). In addition, for CON, all upper-body 1-RM exercises did not change in
comparison with baseline at all other time-points (all P ≥ 0.05).
For BBP 1-RM (see Figure 6.7), a significant GROUP x WEEK interaction was
detected (P ≤ 0.05). At week 8, BBP 1-RM increased in comparison with baseline for
HL-T (13.6%; trivial) and LL-T (8.9%; trivial), but was not different to all other groups.
For SR 1-RM (see Figure 6.7), a significant GROUP x WEEK interaction was detected
(P ≤ 0.05). At week 4, SR 1-RM increased relative to baseline for HL-T (8.8%; trivial)
and was greater than LL-T. At week 8, SR 1-RM remained elevated in comparison with
baseline for HL-T (16.3%; small) and was greater than all other groups. In addition, SR
1-RM was also increased at week 8 in comparison with baseline for BFR-C (7.0%;
trivial), which was greater than CON. Following the de-training period, SR 1-RM
remained elevated at week 12 for HL-T (10.1%; trivial) and was higher than LL-T and
CON.
For BC 1-RM (see Figure 6.7), there was a main effect for WEEK detected (P ≤ 0.001).
When the data was grouped, BC 1-RM was increased at all time-points in comparison
with baseline.

195
Figure 6.7 Normalized (% change
from baseline) lower- and upper-
body 1-RM responses (GROUP x
WEEK interactions; P ≤ 0.05).
Abbreviations: HL-T (heavy-load
resistance training); LL-T (light-
load resistance training); BFR-C
(blood flow restriction with
continuous inflation of cuff
pressure); CON (control).
* indicates significant difference
compared with baseline.
‡ indicates significant difference
compared with week 8.
a indicates significant difference
compared with all other groups.
b indicates significant difference
compared with CON.
c indicates significant difference
compared with BFR-C.
d indicates significant difference
compared with HL-T.
e indicates significant difference
compared with LL-T.
195

196
6.3.3 Muscle mass
6.3.2.1 Duel energy X-ray absorptiometry
Despite being matched for KE 1-RM strength at baseline, body composition (body mass
[BM], lean muscle mass [LM], and fat mass [FM]) was variable between groups, with
any differences between groups being maintained across the duration of the study.
Overall, a significant GROUP x WEEK interaction was observed for BM (P ≤ 0.001),
LM (P ≤ 0.05), and FM (P ≤ 0.001). In addition, a main effect for WEEK was detected
for arm-LM and leg-LM (both P ≤ 0.01). No changes were observed for any parameter
using DXA for CON across the duration of the study period (all P ≥ 0.05). Table 6.3
provides the detailed breakdown of absolute changes observed using DXA for all
groups.
For both absolute and normalized LM, there was a significant increase relative to
baseline at week 8 for HL-T only (2.3%; trivial), which was now greater than LL-T. No
other differences were observed across training weeks.
For both absolute and normalized BM, there was a significant increase relative to
baseline for LL-T (1.7%; trivial) at week 12, but this was not different to all other
groups. This change was likely to be accounted for by an increase in FM, which was
also increased at week 12 in comparison with baseline for LL-T (4.9%; trivial). In
addition, FM was also higher at week 12 in comparison with baseline for HL-T (2.8%;
trivial).

197
Table 6.3 Absolute (kg) change in body composition using Dual X-ray Absorptiometry. Data reported as mean ± SEM.
* different to baseline (P ≤ 0.05).
† different to week 4 (P ≤ 0.05).
‡ different to week 8 (P ≤ 0.05).
a different to all other groups (P ≤ 0.05).
b different to control (P ≤ 0.05).
c different to BFR-C (P ≤ 0.05).
d different to HL-T (P ≤ 0.05).
e different to LL-T (P ≤ 0.05).
BFR-C LL-T HL-T CON
Base-
line
Week 4 Week 8 Week
12
Base-
line
Week 4 Week 8 Week
12
Base-
line
Week 4 Week 8 Week
12
Base-
line
Week 4 Week 8 Week
12
Body
mass
72.4 ±
4.6
72.2 ±
4.6
72.0 ±
4.5
71.8 ±
4.5
74.5 ±
6.7
a
75.1 ±
7.0
a
75.7 ±
7.1
a
77.8 ±
0.5
*†‡cd
71.1 ±
3.6
71.6 ±
3.5
72.1 ±
3.5
72.5 ±
3.7
77.6 ±
4.8
cd
77.5 ±
4.9
cd
78.0 ±
4.9
cd
78.3 ±
4.9
cd
Lean
body
mass
52.3 ±
3.9
a
52.3 ±
4.0
a
52.6 ±
3.8
a
52.5 ±
4.0
a
48.5 ±
3.8
bc
49.1 ±
3.8
bc
48.9 ±
3.7
a
49.2 ±
4.4
bc
49.4 ±
3.2
bc
49.8 ±
3.2
bc
50.4 ±
3.1
*a
49.1 ±
3.4
‡
56.2 ±
4.1
56.5 ±
3.9
57.2 ±
4.3
56.6 ±
3.95
Fat body
mass
16.7 ±
2.2
bd
16.5 ±
2.1
d
16.2 ±
2.0
d
16.2 ±
2.0
a
17.2 ±
4.3
17.3 ±
4.3
d
17.9 ±
4.5
19.7 ±
4.9
*‡b
18.4 ±
2.0
18.6 ±
2.1
18.4 ±
2.1
20.1 ±
1.9
*†‡b
17.7 ±
2.9
17.5 ±
3.1
17.4 ±
2.8
17.9 ±
2.7
Arm lean
mass
6.2 ±
0.6
6.3 ±
0.6
6.3 ±
0.6
6.3 ±
0.6
5.8 ±
0.6
5.9 ±
0.6
5.9 ±
0.6
6.0 ±
0.7
6.1 ±
0.5
6.2 ±
0.5
6.3 ±
0.5
6.12 ±
0.54
7.2 ±
0.7
7.3 ±
0.7
7.3 ±
0.7
7.3 ±
0.7
Leg lean
mass
17.7 ±
1.5
17.9 ±
1.5
17.8 ±
1.5
17.6 ±
1.5
16.3 ±
1.3
16.8 ±
1.3
16.8 ±
1.3
16.4 ±
1.6
16.5 ±
1.1
16.7 ±
1.1
16.7 ±
1.1
16.3 ±
1.1
18.5 ±
1.4
18.3 ±
1.4
18.5 ±
1.5
18.5 ±
1.5
Trunk
lean mass
24.2 ±
1.9
23.8 ±
1.8
23.9 ±
1.6
23.8 ±
1.8
22.1 ±
1.5
22.0 ±
1.7
21.8 ±
1.5
22.6 ±
1.9
22.6 ±
1.6
22.6 ±
1.6
23.0 ±
1.4
22.2 ±
1.6
26.1 ±
1.8
26.3 ±
1.7
26.4 ±
1.8
26.7 ±
1.8
197

198
6.3.2.2 Muscle thickness
Figure 6.8 shows the normalized MTH changes across the duration of the study period
for each group. Absolute and normalized measures for both upper- and lower-body
MTH at baseline were not different between groups, except for biceps brachii whereby
CON was greater than all other groups (P ≤ 0.01). Overall, a significant GROUP x
WEEK interaction was observed for biceps brachii (P ≤ 0.01) and quadriceps (P ≤ 0.05)
MTH only. There were no changes observed for any MTH parameters for CON across
the duration of the study (all P ≥ 0.05).
For both absolute and normalized quadriceps MTH, there was a significant increase at
week 8 relative to baseline for HL-T (14.4%; small) and LL-T (9.8%; trivial). In
addition, both absolute and normalized biceps brachii MTH was also significantly
increased at week 8 relative to baseline for HL-T only (11.5%; small). Following the
de-training period, quadriceps MTH remained elevated at week 12 for HL-T only
(11.5%; small).
There were main effects detected for WEEK whereby triceps brachii, hamstring, and
calf MTH all increased relative to baseline (all P ≤ 0.01; trivial-small). At week 8,
triceps brachii MTH (mean 6.2%), hamstring MTH (mean 7.5%), and calf MTH (mean
5.9%) all increased relative to baseline when the data was grouped. There was also a
trend for pectoralis major MTH to be increased at week 8 relative to baseline (mean
5.9%), but this was not significant (P = 0.063; trivial-small). Following the de-training
period, triceps brachii MTH (mean 5.9%), hamstrings MTH (mean 7.8%), and calf
MTH (mean 4.5%) remained higher at week 12 in comparison with baseline.

199
Figure 6.8 Normalized (% change from
baseline) in MTH.
resistance training); LL-T (light-load
resistance training); BFR-C (blood flow
restriction with continuous inflation of cuff
* indicates significant difference compared
with baseline (P ≤ 0.05).
# indicates TIME effect compared with
baseline (P ≤ 0.05).
b indicates significant difference compared
with CON (P ≤ 0.05).
c indicates significant difference compared
with BFR-C (P ≤ 0.05).
d indicates significant difference compared
with HL-T (P ≤ 0.05).
199

200
6.3.4 Corticomotor responses and training adaptations
There were no differences in the TMS stimulator output for AMT, single-pulse, paired-
pulse, and MMAX between GROUPS at any TIME point across all WEEKS. Therefore
these were averaged across all groups and presented in Table 6.3.
Table 6.4 Baseline corticomotor responses and TMS variables.
TMS Variables measured pre-exercise
Baseline Week 4 Week 8 Week 12
Stimulator output for MMAX
(mA)
64.3 ± 2.7 68.6 ± 2.6 67.3 ± 2.2 69.2 ± 2.7
AMT (% MSO) 43 ± 1 43 ± 1 43 ± 1 42 ± 1
Unconditioned
(single-pulse; % MSO)
51 ± 1 51 ± 2 51 ± 2 50 ± 2
Conditioning
(paired-pulse; % MSO)
34 ± 1 35 ± 1 35 ± 1 33 ± 1
AMT, active motor threshold; Maximal rmsEMG, maximal root mean squared
electromyography; MMAX, maximal compound peripheral muscle action potential, MSO;
maximal stimulator output. Data reported as mean ± SEM.
6.3.4.1 Isometric strength characteristics
There were no differences in pre-exercise MVIC at baseline between groups, and in
addition, pre-exercise MVIC was not different between GROUPS or across WEEKS
(i.e. no change in isometric knee extension strength). However, a significant main effect
for TIME (P ≤ 0.001) was observed whereby it appeared that MVIC was higher at pre-
exercise in comparison with all other time points post-exercise (Figure 6.9).

201
Figure 6.9 Maximal
voluntary isometric
contraction responses
measured acutely across
the duration of the 12
week study.
Abbreviations: HL-T
(heavy-load resistance
training); LL-T (light-load
resistance training); BFR-
C (blood flow restriction
with continuous inflation
of cuff pressure); CON
(control).
# indicates significant
effect vs pre-exercise (P ≤
0.001).
201

202
6.3.4.2 Maximal compound muscle action potential
There were no differences in pre-exercise MMAX at baseline between HL-T, LL-T, and
CON. However, pre-exercise MMAX was higher at baseline in comparison with all
groups, and this remained the same throughout the duration of the study period. A
significant main effect for TIME (P ≤ 0.01) and GROUP x TIME interaction (P ≤ 0.01)
was observed (Figure 6.10). Post hoc analyses revealed that there were no differences in
post-exercise MMAX in comparison with pre-exercise for LL-T, BFR-C, and CON in
comparison with baseline. Conversely, MMAX was decreased at 5 min and 30 min post-
exercise compared with pre-exercise for HL-T. In addition, MMAX was higher at all
post-exercise time-points for BFR-C in comparison with all groups.

203
Figure 6.10 Maximal
compound muscle action
potential responses measured
acutely across the duration
of the 12 week study.
Abbreviations: HL-T
resistance training); BFR-C
# indicates significant effect
vs pre-exercise (P ≤ 0.01).
a indicates significant effect
vs all other groups (P ≤
0.01).
203

204
6.3.4.3 Corticomotor excitability
There were no differences in pre-exercise MEP amplitude within GROUPS across the
duration of the training programme (P ≥ 0.05). However, pre-exercise MEP amplitude
was higher for LL-T and CON in comparison with HL-T and BFR-C (P ≤ 0.05).
Therefore, the data is presented as normalized relative to pre-exercise amplitudes
(Figure 6.11).
Overall, a significant main effect for TIME (P ≤ 0.001) and WEEK (P ≤ 0.01) were
detected, as well as GROUP x TIME (P ≤ 0.001), GROUP x WEEK (P ≤ 0.001), and
GROUP x TIME x WEEK (P ≤ 0.001) interactions were observed for MEP amplitude.
Post hoc analyses revealed that MEP amplitude was higher for HL-T in comparison
with CON. In addition, relative to pre-exercise MEP amplitude was increased at 5 min
post-exercise for both BFR-C (mean 47.8%) and HL-T (mean 86.7%). At 30 min post-
exercise, MEP amplitude was higher for HL-T in comparison with all other groups,
while BFR-C was greater than CON. Furthermore, MEP amplitude remained higher
relative to pre-exercise for BFR-C (mean 41.5%) and HL-T (mean 96.8%). At 60 min
post-exercise, MEP amplitude was higher at 60 min post-exercise for HL-T in
comparison with LL-T and CON only, while BFR-C remained higher than CON. In
addition, MEP amplitude remained significantly higher than pre-exercise for HL-T only
(mean 58.5%). There were no acute changes in MEP amplitude at any time-point across
the duration of the training program for LL-T or CON.

205
Figure 6.11 MEP
amplitude relative to
MMAX following
resistance exercise.
Abbreviations: HL-T
(heavy-load
resistance training);
LL-T (light-load
BFR-C (blood flow
restriction with
continuous inflation
of cuff pressure);
CON (control).
* indicates
significantly different
to Pre-exercise (P ≤
0.05).
a indicates
to all others trials (P
≤ 0.05).
b indicates
to CON (P ≤ 0.05).
c indicates
to BFR-C (P ≤ 0.05).
d indicates
to HL-T (P ≤ 0.05).
e indicates
to LL-T (P ≤ 0.05).
205

206
6.3.4.4 Stimulus response curve
Changes in MEP amplitude at all points along the recruitment curve were investigated
prior to and following the intervention. There was no significant difference in MEP
amplitude between training groups at baseline at any points along the recruitment curve
(all P ≥ 0.05; Figure 6.12). However, there were some differences for the CON group.
A main effect for WEEK (P ≥ 0.001) and GROUP x WEEK interaction (P ≥ 0.001) was
detected for 100% AMT. Post hoc analysis revealed that AMT was higher at baseline
for BFR-C and CON in comparison with HL-T and LL-T.
A main effect for GROUP (P ≤ 0.05) and WEEK (P ≤ 0.05) was detected for peak-to-
valley MEP amplitude at 150% AMT. In addition, there was a trend for a GROUP x
WEEK interaction, however this was not significant (P = 0.056). Post hoc analyses
revealed that week 4 was different to week 8 and 12, and this appeared to be driven by a
CON being greater than all other groups.
A main effect for GROUP (P ≤ 0.05) and WEEK (P ≤ 0.05) was detected for peak-to-
peak MEP amplitude at 170% AMT. Post hoc analyses revealed that CON was higher
than HL-T, and this appeared to be driven by week four being higher than all other
weeks.

207
Figure 6.12
Stimulus response
curves for all groups
expressed as a
percentage of MMAX.
Abbreviations: HL-T
(heavy-load
LL-T (light-load
BFR-C (blood flow
restriction with
continuous inflation
of cuff pressure);
CON (control).
b indicates
significantly
different CON (P ≤
0.05).
c indicates
significantly
different to BFR-C
(P ≤ 0.05).
d indicates
significantly
different to HL-T (P
≤ 0.05).
207

208
6.3.4.5 Short-interval intracortical inhibition
There were no main effects for GROUP (P = 0.19), WEEK (P = 0.88) or TIME (P =
0.94) detected for SICI, and so no interactions were revealed (Figure 6.13). Therefore,
there were no acute changes in SICI within a testing session, or across weeks.
Furthermore, there were no significant differences in SICI at baseline between groups at
any week (all P ≥ 0.05), therefore, no chronic adaptations in SICI were observed.

209
Figure 6.13 Short interval
intracortical inhibition for
all groups.
Abbreviations: HL-T
resistance training); BFR-C
209

210
6.4 Discussion
The present study examined the acute responses in corticomotor excitability and
inhibition to BFR-RT in comparison with more traditional resistance training
techniques, while also examining these responses over an eight week training and four
week de-training period. The major findings showed that (i) corticomotor excitability
was increased acutely post-exercise for BFR-C (30 min) and HL-T (60 min), but SICI
remained unaffected; (ii) no chronic adaptations in corticomotor excitability or SICI
were found across the duration of the training and de-training programme, regardless of
training group; and (iii) muscle strength and mass increased for BFR-C to different
degrees for each exercise/muscle group similarly to LL-T, and overall appeared to be
lower in comparison with HL-T. These results partially support the hypothesis, and
suggest that while beneficial adaptations in muscle strength and mass occur following
full-body resistance training with continuous low-pressure BFR, this was not driven by
changes in corticomotor plasticity as measured via TMS.
6.4.1 Acute responses in corticomotor plasticity
Results from the current study showed that continuous BFR in combination with KE
exercise at 20% 1-RM rapidly increased MEP amplitude (at 5 min post-exercise) and
remained elevated for up to 30 minutes post-exercise. The acute increase in MEP
amplitude was greater in comparison with CON, and similar to HL-T. In addition, there
were no changes in SICI post-exercise for any trial at any time-point immediately post-
exercise. These findings were similar to those observed in chapter four; however, MEP
amplitude was found to be increased for up to 60 min post-exercise following low-
pressure continuous BFR-RE of the upper-body compared with a 30 min increase
following BFR-RE of the lower-body in the current study. It is likely that the

211
differences between the current study and chapter four can be explained by different
resistance exercises performed (knee extension versus elbow flexion, respectively) and
muscle groups measured (quadriceps versus biceps brachii, respectively), as the relative
load (20% 1-RM), volume (30/15/15/15 repetition scheme), and relative BFR pressure
and duration were similar between studies. Overall, regardless of the total duration of
time that MEP amplitude was increased post-exercise, the combined results from the
current study and chapter four suggest that performing BFR-RE can modulate the
excitatory corticospinal circuits at the level of the M1, because both rmsEMG and
MMAX did not change post-exercise, indicating that peripheral mechanisms were not
likely responsible for this acute increase in MEP amplitude. Taken together with the
results from the current study and chapter four, these data suggest that the M1 is acutely
activated to a greater extent under resistance exercise conditions with BFR compared
with LLRE and non-exercise controls, and similar to HLRE. The stimuli responsible for
this response could possibly be accounted for by altered sensory feedback to cortical
and/or subcortical areas via group III and IV muscle afferent fibres as previously
suggested (Moritani et al., 1992, Karabulut et al., 2007, Yasuda et al., 2010a).
The current study used a unique TMS testing protocol whereby the neuromuscular
responses were not only measured acutely following a single bout of KE exercise at a
single time-point, but were also measured acutely at different time-points across the
duration of the training and de-training programme. This type of testing protocol may
allow an insight in to the chronic adaptations that occur following an acute resistance
exercise bout. It was therefore interesting to note that MEP amplitude increased post-
exercise for both HL-T and BFR-C to different degrees throughout the duration of the
training period. While post hoc analysis was unable to detect at which week this
occurred, it appeared to be driven by the elevated MEP amplitude occurring at baseline

212
(i.e. prior to beginning training), because the post-exercise response at week four and
week eight appeared to be attenuated in comparison (see Figure 6.10). While the exact
reason for the attenuated MEP amplitude post-exercise following training is unknown,
the author hypothesize that this could be attributed to one of several factors.
Firstly, MEP amplitude has been shown to be facilitated during the initial post-exercise
period (i.e. within the first 5 minutes) following fatiguing MVICs (Lentz and Nielsen,
2002, Ljubisavljević et al., 1996). Considering that post-exercise MVIC was decreased
post-exercise for all groups in the current study, and MMAX was reduced post-exercise
for HL-T, the initial increase in MEP amplitude for BFR-C and HL-T may be attributed
to central fatigue mechanisms (Gandevia, 2001). Furthermore, because the exercise
loads and BFR protocol used during TMS testing remained the same throughout the
duration of the study for each group, and KE 1-RM strength was increased following
training, it is possible that the acute post-exercise response at week four and week eight
were attenuated due to reductions in central fatigue as an adaptation to the
exercise/testing protocol. Another plausible explanation for this attenuation in acute
post-exercise MEP amplitude at week four and week eight in comparison with baseline
may be as a result of motor memory consolidation, a phenomenon first proposed in
1900 (Müller and Pilzecker, 1900). During an initial testing session, relatively large
areas of the M1 are activated while learning a new task, as evidenced by both TMS and
positron emission tomography (PET) (Pascual-Leone et al., 1995, Shadmehr and
Holcomb, 1997). During this initial phase of learning, movements are unskilled, highly
feedback dependent and require strong attentional demands, which increases the
centrally challenging demand on the neuromuscular system. With chronic repetition and
learning of the task (i.e. training), feedback becomes less important while the accuracy
and velocity of the movement increase, resulting in the performance eventually
becoming “automatic” (Pascual-Leone et al., 1994). When this happens, M1 activity

213
becomes more localized and moves to other sites within the CNS (similar to the
mechanisms involved in use-dependent long-term potentiation (Jacobs and Donoghue,
1991)). For example, TMS motor mapping shows larger cortical motor areas over the
course of five days of learning a new motor skill (Pascual-Leone et al., 1995), while
PET and MRI studies reveal a shift in activity from pre-frontal regions of the cortex to
premotor, posterior parietal and the cerebellum (Shadmehr and Holcomb, 1997, Seidler,
2010). This rapid time-course (lasting several minutes to several hours) may modulate
M1 cortical outputs via unmasking of existent but latent neuronal connections,
increasing its influence on a motoneuron pool and an overall net increase in
corticospinal plasticity. While the current study provides no evidence for this
phenomenon, changes in plasticity within other cortical areas or subcortical areas
cannot be ruled out, and it would seem a reasonable conclusion based on the current
findings.
6.4.2 Chronic adaptations in corticomotor plasticity
In order to determine the potential neuromuscular adaptations responsible for the
increase in strength that has previously been observed following BFR-RT, this study
measured the time-course adaptations in corticomotor excitability and inhibition over
the duration of a BFR training and de-training programme. While a single bout of KE
exercise with continuous BFR induced an acute increase in MEP amplitude post-
exercise, properties of the stimulus response curve (a measure of corticomotor
excitability) were not modified following four and eight weeks for BFR-C. However,
this was also the same for all groups, despite significant increases in KE 1-RM strength.
This result was unexpected given the acute increase in MEP amplitude observed for
BFR-C and HL-T, and also previous observations using the same technique that showed

214
HLRT produces significant increases in corticomotor excitability (Goodwill et al., 2012,
Leung et al., 2015) and reductions in inhibition (Latella et al., 2012, Weier et al., 2012).
In addition, considering that quadriceps MTH and leg-LM were not increased for BFR-
C throughout the training period, it is plausible to expect that the significant increase in
KE 1-RM strength observed may be accounted for by neural adaptations, however, this
was not evident in the current study.
Previous studies examining acute and chronic neuromuscular adaptations following
BFR-RT programs have reported mixed findings. Acute EMG studies have revealed
that BFR-RE increases muscle activity greater than load matched controls (Takarada et
al., 2000c, Yasuda et al., 2006, Moritani et al., 1992, Yasuda et al., 2009), and similar to
HLRE (Loenneke et al., 2014d, Takarada et al., 2000c), suggesting increased neural
drive to the muscle. However, with regards to chronic responses, using the twitch
interpolation technique, Moore et al., (2004) observed no change in maximal motor unit
activation following eight weeks of elbow flexion training, while Kubo et al., (2006)
also reported no change following 12 weeks of knee extension training. Therefore, the
observation that corticomotor plasticity was not modified following eight weeks of
BFR-C in the current study is in agreement with previous BFR-RT literature examining
neuromuscular adaptations. However, the data examining corticomotor adaptations
following BFR-RT are limited, and it is difficult to draw many conclusions as to what
effect BFR has on central nervous system adaptations based on current observations.
Considering that KE 1-RM strength increased similarly for BFR-C and HL-T following
training, and there is now a large amount of evidence to indicate that HLRT of the
upper- and lower-body modifies corticomotor plasticity, it is important to discuss the
previous TMS literature examining these adaptations to explain the results of the
current study.

215
The use of TMS to investigate corticomotor adaptations to motor training and HLRT
has been around since the early 21st
century (Carroll et al., 2002), and since this time
has produced varying results following resistance training interventions. For example,
Goodwill et al., (2012) reported a 41% increase in quadriceps strength following three
weeks of HLRT (single leg squat) which was accompanied by a 55% increase in MEP
amplitude. However, in agreement with the current study, Latella et al., (2012) observed
no change in MEP amplitude following eight weeks of HLRT (leg press) despite a
similar 22% increase in quadriceps strength. Others have shown that the increase in
muscle strength following HLRT may be due to a modification in intracortical
inhibition, identified via reductions in SICI or the cortical silent period (Latella et al.,
2012, Weier et al., 2012). However, in agreement with the results from the current
study, corticomotor inhibition has also been shown not to be modified following HLRT
(Hortobágyi et al., 2011). The TMS technique has some limitations in that changes in
MEP amplitude and SICI are not only affected by the excitability of the M1, but also of
motoneurons at the level of the spinal cord (Carroll et al., 2001, Classen et al., 1998).
Therefore, it is possible that adaptations in spinal mechanisms or other cortical
structures could have contributed to the increase in muscle strength following training
for all groups. For example, techniques such as cervicomedullary MEPs, transcranial
electrical stimulation, Hoffman reflex, and the Volitional wave can be used to measure
spinal cord excitability and motor unit activation following exercise/training
interventions. In fact, recent evidence has shown that spinal excitability is enhanced
immediately post-exercise and also following HLRT interventions in untrained
populations similar to those in the current study (Nuzzo et al., 2015). Based on the
current results, while there was no chronic modification in corticomotor plasticity
observed using TMS, perhaps adaptations occurred elsewhere along the corticospinal

216
tract that remain undetected. Future studies should attempt to measure changes in
neurophysiological properties using these techniques in order to quantify the effect of
BFR-RT in relation to both LLRT and HLRT.
6.4.3 Adaptations in muscle strength and mass
Results from the current study showed that an eight week, thrice weekly training
protocol consisting of three lower-body and three upper-body exercises produced
significant increases in maximum strength and MTH. However, the magnitude of these
effect sizes in untrained subjects was trivial-small (Rhea, 2004), and it appeared that
traditional HL-T resulted in greater increases in muscle strength and MTH in
comparison with all groups, while the adaptations were similar for BFR-C and LL-T.
These findings do not support the use of a full-body resistance training program with
BFR to enhance muscle strength and mass in healthy young populations compared with
more traditional HLRT.
The present study found mostly no significant differences in muscle strength and mass
measurements between BFR-C and LL-T following training, however, only SQ 1-RM
strength was greater for LL-T in comparison with BFR-C (24.1% versus 11.3%,
respectively). In contrast, the majority of previous studies comparing the change in
muscle strength and mass have generally shown that the adaptations are greater
following BFR-RT in comparison with load matched controls (Takarada et al., 2000c,
Yasuda et al., 2010b, Patterson and Ferguson, 2010). The focus of these studies has
mainly been on adaptations in muscle strength and mass following single-joint exercises
that comprises of training with relatively small muscle mass involvement (e.g. knee and
elbow flexion/extension (Takarada et al., 2000c, Moore et al., 2004, Kubo et al., 2006).

217
As recommended by the American College of Sports Medicine, a resistance training
program should contain numerous exercises for both the upper- and lower-body in order
to induce maximal gains in muscle strength and mass (ACSM, 2013, Baechle and Earle,
2008). Therefore, a novel aspect of the current study was that all participants completed
a full-body resistance training programme. This effectively increased the total volume
of work (sets x repetitions) performed across a large amount of muscle groups that may
have been involved in more than one exercise (e.g. increased quadriceps muscle
involvement with the combination of KE and SQ). Given there exists a strong
possibility for a dose-response relationship between muscular adaptations and resistance
training volume, at least up to a certain volume (Martín‐Hernández et al., 2013), it is
probable that the similarities in strength and mass between training groups can be
explained by the increased total volume of work performed. Additionally, there is some
evidence to suggest that training for longer training durations (≥ 8 weeks) produces
similar muscular adaptations for LLRT with and without BFR (Fitschen et al., 2013,
Burgomaster et al., 2003, Weatherholt et al., 2012, Barcelos et al., 2015), which may in
part explain the results in the current study.
Importantly, this study also compared the effects of BFR-RT to traditional HLRT.
Previous studies have produced similar (Takarada et al., 2000c) or decreased
(Lixandrão et al., 2015, Yasuda et al., 2010c) adaptations for BFR-RT in comparison
with HLRT. These differences are possibly attributed to variances in exercise
interventions, BFR variables, testing protocols, and participant cohort. In agreement, the
current study showed mixed results, with some exercises and muscle groups increasing
similarly between groups in 1-RM strength and muscle mass, however, overall it
appeared that HL-T had the most beneficial effect in comparison with all other groups.
To highlight this, the main outcome exercise for the study was KE, which increased

218
similarly for BFR-C and HL-T following training (20.1% and 25.8%, respectively).
Despite this, quadriceps MTH was increased by 14.4% in HL-T only, with no change
detected for BFR-C. In addition, SR 1-RM was also significantly greater for HL-T
(16.6%) in comparison with BFR-RT (6.9%) and LL-T (3.9%). Therefore, based on the
results from the current study, it appears that BFR-RT and LLRT were less effective in
comparison with traditional HLRT for developing muscle strength and mass in healthy
young populations. It is possible that the total volume of work (set x repetitions x load)
was too low for BFR-C and LL-T to induce significant muscular adaptations. In
addition, none of the resistance exercise protocols included repetitions to muscle failure,
which has been shown to be effective at inducing significant increases in both muscle
strength and mass for both traditional resistance training and BFR-RT. Consequently,
this may not have been the best way to apply this technique in this population. For
example, BFR may be better suited for healthy individuals as a supplement to their
traditional HLRT to the end of their workouts (Yamanaka et al., 2012, Luebbers et al.,
2014). Additionally, another alternative would be to combine traditional HLRT with
BFR-RT throughout a periodised training week, a method which has been shown to be
more than BFR-RT alone (Yasuda et al., 2010c). While the results of this study support
the use of HLRT to develop muscle strength and mass in young healthy untrained
populations, it may be expected that for individuals unable to lift heavy-loads (e.g. the
elderly, following musculoskeletal injury, or where muscle atrophy and weakness occur
due to the effects of inactivity or disease), that BFR-RT or indeed LLRT may be a more
preferential exercise modality.
Although increases in some of the muscle strength and mass measurements following
eight weeks of resistance training were observed, the changes were not as significant as
previous studies and should thus question the training protocols used in the current

219
study in order to explain the results. Previously, arbitrary BFR pressures and pressures
set according to resting blood pressure (e.g. 1.3 x systolic blood pressure) were applied
when performing BFR-RT; however, more recent evidence suggests that the BFR
pressure utilized should be individualized for each participant (Loenneke et al., 2014c).
The final BFR pressure for each participant in the current study was equal to 60% of the
maximal limb arterial occlusion pressure, measured using LOP technology. While a
range of 50-80% LOP has been recommended and used previously (Loenneke et al.,
2014d), it is currently not known what the most “optimal” BFR pressure is to induce
beneficial muscular adaptations. Pressures as low as 50 mmHg during BFR-RT have
been shown to increase muscle strength and cross-sectional area greater than LLRT
(Sumide et al., 2009), while a more recent study showed similar adaptations in muscle
strength and endurance following eight weeks of LLRT with either 40% or 90% arterial
occlusion pressures (Counts et al., 2015). Furthermore, BFR-RT has been shown to
improve muscle strength and mass at loads as low as 15% MVIC (Kacin and Strazar,
2011), while in some instances, similar improvements have been shown to occur
between loads ranging from 20 to 50% 1-RM (Barcelos et al., 2015). Based on this
information, it is likely that the participants were training at a sufficient BFR pressure
and resistance training load throughout the study. Additionally, our resistance training
protocol consisted of three exercises for both the lower- and upper-body for 3-4 sets,
which was completed three times per week. This may have resulted in a greater training
stimulus for LL-T in the current study in comparison with previous studies that used
different training frequencies (i.e. ranging from twice daily (Yasuda et al., 2005, Abe et
al., 2006, Ohta et al., 2003, Yasuda et al., 2010b)) to three times per week (Counts et
al., 2015, Fitschen et al., 2013)), durations (i.e. 1-12 weeks) (Abe et al., 2005a, Fujita et
al., 2008b, Kubo et al., 2006), fewer total repetitions (Martín‐Hernández et al., 2013),
and single exercise protocols (Takarada et al., 2000c). Partial blood flow occlusion due

220
to muscle contractions for HL-T and LL-T cannot be ruled out either, considering the
repetitions were completed slowly and controlled by an external metronome, whereas
most previous studies often do not report the repetition timing. It is plausible that the
increased time under tension would have increased muscle activity, metabolic stress,
and induced a level of hypoxia similarly between all training groups; however, these
measurements were out of the scope of the current study and should be investigated in
future. A heterogeneous population of males and females were recruited for the study
and while previous BFR-RT studies have shown no differences in muscular adaptations
between genders (e.g. Fitschen et al., 2008), a statistical comparison was not made as
the experiment was powered to find differences between the total group numbers
recruited, and not between genders. Finally, untrained participants were used in the
current study, and while the author attempted to control for any potential learning
effects during familiarisation, a limitation of the current study is that a short training
period prior to the intervention was not conducted due to time constraints. Therefore,
the author cannot rule out a motor learning effect, or high/low individual responders
(Mann et al., 2014) which may have influenced the strength measurements due to
repeated exercise training and testing, however this was the same for all groups.
6.4.4 Effects of de-training on neuromuscular function
While research has shown that muscle strength and mass can be maintained following
short periods (≤ 4 weeks) of de-training following the completion of BFR-RT, it is
unknown whether full-body resistance training with BFR results in similar adaptations.
Following the four week de-training period in the current study, only KE 1-RM
remained higher in comparison with baseline for BFR-C, while all other resistance
exercises returned to baseline levels. Previously, Yasuda et al. (2014a, 2015) has shown
that lower-body strength can be maintained for longer de-training periods (12-24

221
weeks) following BFR-RT in comparison with the current study; however, those studies
were performed with older adults (≥ 60 yrs). Therefore, this was the first study to
observe that lower-body 1-RM strength can be maintained following short periods of
de-training from BFR-RT in young healthy populations. While this result may prove
beneficial to those that require short periods away from their training programmes, it is
important to note that the maintenance of strength following BFR-C was not different to
HL-T or LL-T. Regarding the upper-body, strength returned to baseline levels following
the de-training period for BFR-C, a result which is in contrast to previous studies
(Yasuda et al., 2014b, Yasuda et al., 2014c). For example, Yasuda et al., (2014b) had
subjects perform bench press exercise with BFR for six weeks which resulted in a
significant 4.3% increase in 1-RM strength and remained elevated by 4.9% following
three weeks of de-training. Upon closer examination, the percent change in upper-body
1-RM strength in the current study was not significant for BFR-C, therefore it would
appear that if a greater increase in 1-RM strength occurred following training then these
adaptations may have been maintained after four weeks of de-training.
Of the previous studies reporting the effects of de-training following BFR-RT, while
strength has been shown to be maintained, muscle mass appears to return to baseline
levels despite a significant increase following training (Yasuda et al., 2014b, Yasuda et
al., 2014a). So far, authors have speculated that the maintenance of strength following
both BFR-RT appears to be driven by neuromuscular adaptations. However, results
from the current study do not support this, as there was no chronic modulation in
corticomotor plasticity observed following resistance training (either with or without
BFR) or at week 12 following the de-training period. While the limitations of the TMS
testing in this study have already been discussed, it is therefore possible that other
cortical and spinal structures are responsible for the maintenance of KE 1-RM strength
for BFR-C following the de-training period. In addition, both KE 1-RM strength and

222
quadriceps MTH remained elevated for HL-T at week 12, therefore it is probable that
changes in muscle architecture were also responsible for strength maintenance for HL-
T, similarly to previous literature (Hakkinen et al., 2000, Narici et al., 1989).

223
6.5 Conclusion
In conclusion, the overall change in muscle strength and mass following eight weeks of
full-body resistance training was similar for BFR-C and LL-T, while it appeared that
the increase was greatest for HL-T. However, these adaptations were considered trivial-
small in healthy untrained individuals. Furthermore, an acute bout of knee extension
exercise with BFR increased corticomotor excitability for up to 30 minutes post-
exercise, similar to HL-T. However, there were no chronic adaptations observed in
corticomotor excitability or inhibition following training, but this was the same for all
groups. Based on these results, the use of TMS was unable to determine the underlying
neuromuscular adaptations following BFR-RT in the current study that may have been
responsible for the increase in muscle strength for the quadriceps muscle group.
Therefore, future investigations should utilize other techniques to measure changes in
neuroplasticity, particularly at the spinal level, in order to better understand the
neuromuscular adaptations that occur following BFR-RT that may underpin adaptations
in muscle strength, similar to the responses observed following traditional HLRT.

224
CHAPTER SEVEN:
Haemodynamic and perceptual adaptations
following blood flow restriction training and
de-training

225
7.1 Introduction
The use of blood flow restriction (BFR) during an acute bout of resistance exercise
(BFR-RE) has been shown to induce haemodynamic and perceptual responses to levels
between those observed for heavy-load resistance exercise (HLRE) and light-load
resistance exercise (LLRE) (Loenneke et al., 2010a, Rossow et al., 2012, Vieira et al.,
2014, Downs et al., 2014). Given the likelihood that BFR resistance training (BFR-RT)
develops muscle strength and mass, the interest in more long-term haemodynamic and
perceptual adaptations to training has grown. However, despite our understanding of the
acute haemodynamic and perceptual responses to BFR-RE, much less is known about
the chronic adaptations that occur following a BFR-RT programme.
The training related haemodynamic adaptations following heavy-load resistance
training (HLRT) have been well characterised (Fleck, 1992, Kelley and Kelley, 2000),
and include beneficial adaptations such as reductions in resting heart rate (HR) and
blood pressure (BP), as well as limiting the peak-exercise response in HR and BP
following training periods greater than four weeks (Carter et al., 2003a, Fleck, 1988,
Hagberg et al., 1984, Katz and Wilson, 1992, Kelley and Kelley, 2000, Lovell et al.,
2009, Tsutsumi et al., 1997). While several studies have investigated the impact of BFR
on chronic haemodynamic adaptations following aerobic walking (Park et al., 2010,
Ozaki et al., 2011a) and cycling (Corvino et al., 2014) training, much less is known
about these adaptations following short- and long-term BFR-RT (Fahs et al., 2011a,
Kacin and Strazar, 2011, Kim et al., 2009, Ozaki et al., 2012). Overall, these BFR-RT
studies have reported mixed findings regarding chronic haemodynamic adaptations,
with some showing positive adaptations (Fahs et al., 2011a, Satoh, 2011), or no change
(Kim et al., 2009, Ozaki et al., 2012, Fahs et al., 2011a) in resting and peak-exercising
haemodynamics. For example, resting HR does not appear to become reduced following

226
three (Kim et al., 2009) and four (Kacin and Strazar, 2011) weeks of BFR-RT, while
resting BP has been shown to decrease (Fahs et al., 2011a, Satoh, 2011), increase
(Kacin and Strazar, 2011), or not change (Kim et al., 2009). In addition, it appears that
only one study has examined the peak-exercising responses during BFR-RE before and
after a training period (Kacin and Strazar, 2011). In the study by Kacin and Stazar
(2011), while muscle endurance (measured via repetition to volitional fatigue) increased
following four weeks of knee extensor training with BFR, there were no chronic
adaptations in HR and BP observed, suggesting that the increase in exercise
performance may have been mediated by peripheral vascular adaptations as examined
in other studies (Evans et al., 2010, Kim et al., 2009, Horiuchi and Okita, 2012, Hunt et
al., 2013, Fahs et al., 2013b, Downs et al., 2014). In addition, BFR-RE is also known to
result in an increased rating of perceived exertion (RPE) and pain in comparison with
light-load exercise without BFR (Hollander et al., 2010, Loenneke et al., 2010a,
Wernbom et al., 2006, Wernbom et al., 2009, Vieira et al., 2014, Fitschen et al., 2013,
Rossow et al., 2012). Furthermore, results from chapter four showed that BFR-RE
produced similar levels of RPE and pain as traditional HLRE. While the high acute
increase in perceptual responses may limit the use of BFR in some clinical populations,
there is promising evidence that shows the elevated RPE and pain response are
decreased over the length of a training program (Fitschen et al., 2013), possibly
indicating a repeated bout effect (Wernbom et al., 2012b, McHugh, 2003).
Based on the available data, it is currently uncertain as to whether BFR-RT provides
beneficial adaptations in resting and exercising haemodynamics. Furthermore, it is
difficult to compare the results within these studies due to different BFR methods
employed, and also differences in muscles trained, training frequency and duration.
Most of these studies thus far may be limited in the fact that they only examined

227
haemodynamic and perceptual responses following single joint, small muscle mass type
resistance training (e.g. elbow or knee flexion/extension). It may be plausible to expect
that with more muscle mass involvement, and longer duration resistance exercise
sessions involving greater training volumes (i.e. sets x repetitions) that greater
adaptations may occur following a full-body resistance training programme similar to
those reported following HLRT (Fleck, 1988, Hagberg et al., 1984, Katz and Wilson,
1992, Kelley and Kelley, 2000, Lovell et al., 2009, Tsutsumi et al., 1997) and aerobic
training with BFR (Park et al., 2010, Ozaki et al., 2011a, Corvino et al., 2014) or
without BFR (Carter et al., 2003a). If this hypothesis is indeed correct, it would provide
further evidence that BFR-RT should be considered as an alternative to HLRT for
development of muscle strength and mass, while also prescribed as a beneficial training
method to stimulate cardiovascular adaptations and reduced perceptual responses for
healthy and clinical populations.
Therefore, the aim of this study was three fold; (i) to investigate the acute
haemodynamic and perceptual responses to an acute bout of BFR-RE of the knee
extensors; (ii) to investigate the time-course training and de-training related
haemodynamic and perceptual adaptations to a full-body BFR-RT programme; and (iii)
to compare these results to more traditional resistance training programmes such as
HLRT and LLRT. It was hypothesised that both BFR-RT and LLRT will produce
similar acute increases in HR, BP, and Q̇ , with these values being lower than HLRT. In
addition, the peak exercising HR and BP would be reduced following the eight week
training programme. Regarding perceptual responses, it was hypothesised that both
RPE and pain are greatest with BFR-RT and HLRT, but these responses would improve
(i.e. decreased RPE and pain) over the training programme due to the repeated bout
effect.

228
7.2 Methods
The data collected within this study chapter were taken in conjunction with the methods
reported in chapter six as part of a larger study. While chapter six examined the
neuromuscular, muscle strength and mass adaptations to training and de-training, the
methods presented within this chapter focuses on haemodynamic and perceptual
adaptations to training and de-training. Therefore, much of the technical methodology
(e.g. participants, experimental design, resistance training programme, and the BFR
protocol) are identical and will be referred to accordingly.
7.2.1 Participants
The participants recruited for this study were identical to chapter six, and the reader is
directed to section 6.2.1 (page 172) for more information.
The experimental design for this study was identical to chapter six, and section 6.2.3
(page 173). Briefly though, it is important to remind the reader that following random
allocation, participants in the resistance training groups (HL-T, LL-T, and BFR-C) as
well as control (CON) reported to the laboratory and undertook baseline testing that
included haemodynamic testing (see section 7.2.6, page 229) for the knee extension
(KE) exercise as the main outcome measure for strength. Testing occurred at rest prior
to exercise, as well as during the final repetitions of the last exercise set to measure the
maximal peak-exercise response. In addition, RPE and pain responses (see section
7.2.7, page 230) were collected 5 minutes following completion of KE exercise, prior to
neuromuscular testing. Figure 6.1 (page 175) shows the overall timeline for the
experimental protocol, and Figure 6.2 (page 177) details an example of the acute

229
neuromuscular, haemodynamic, and perceptual responses that were taken within a
single testing session. Thereafter, participants completed the same resistance training
programme as described in chapter six (section 6.2.4, page 178), as well as repeating
haemodynamic and perceptual testing at the mid-point of the training programme (week
4) and at completion (week 8), as well as following the de-training period (week 12).
7.2.3 Anthropometrics
Anthropometric data collected were identical to chapter six (see section 6.2.2, page
173).
7.2.4 Resistance training programme
The resistance training programme for this study was identical to chapter six. For a
more detailed description, refer to chapter six, and section 6.2.4 (page 178).
The BFR protocol used for this study was identical to chapter six. For a more detailed
description, refer to chapter six, and section 6.2.4.3 (page 179).
7.2.6 Measurement of haemodynamic variables
The haemodynamic measurements for KE exercise (see Figure 7.1) were HR, blood
pressure (systolic BP, diastolic BP) and Q̇ , while MAP, SV, TPR, and RPP were
calculated following data collection. Refer to chapter three, section 3.6 (pages 110-112)
for a more detailed description of the general methods employed. All measurements
were taken pre-exercise at rest and at peak-exercise to measure the acute
haemodynamic responses, as well any chronic training related adaptations as measured
over the training weeks.

230
Figure 7.1 Participant and equipment set up for haemodynamic testing prior to knee extension
exercise. a represents the Innocor metabolic cart, providing visual feedback and results on the
computer monitor, which is measured at b via re-breathing method; c represents the lead author
conducting blood pressure measurement on the participants non-exercise arm with a standard
blood pressure cuff and stethoscope.
Perceptual responses measured for this study (RPE and pain) were collected according
to procedures described in the general methods. For a more detailed description, refer to
chapter three, and section 3.7.1 (page 113).
a
b
c

231
All data for measured variables were found to be normally distributed as assessed with
a Shapiro-Wilks test (P ≤ 0.05). Statistical analyses were performed by two way
repeated measures ANOVA for GROUP (HL-T; LL-T; BFR-C; CON) x TIME (rest;
peak-exercise) x WEEK (baseline; week 4; week 8; week 12). As CON did not
complete measurements during at the peak-exercise time-point for haemodynamic
responses, or for perceptual responses to resistance exercise, this group was excluded
from the analysis for the dependent variables mentioned, and the analysis was
performed using all other groups. Significant main effects and interactions were further
examined via a Tukey-Kramer post hoc test to determine differences for each dependent
variable. All statistical procedures were performed using NCSS statistical software
(version 2007). The level of significance was set at P ≤ 0.05 and all data are presented
as mean ± standard error of the mean (SEM) unless stated otherwise.

232
7.3 Results
7.3.1 Haemodynamic adaptations
7.3.1.1 Cardiac output
There were no differences for Q̇ between groups at rest at baseline, and this remained
constant across the duration of the study (all P ≥ 0.05; Figure 7.2). A main effect for
TIME (P ≤ 0.0001) was detected whereby Q̇ increased from rest to peak-exercise for
HL-T, LL-T, and BFR-C, but there were no differences between groups. There was a
trend for Q̇ to be higher at baseline in comparison with all other weeks, however this
was not significant (P = 0.089).

233
Figure 7.2 Cardiac output for all
groups across the duration of the
training programme.
resistance training, ●); LL-T
(light-load resistance training, ○);
BFR-C (blood flow restriction
with continuous inflation of cuff
pressure, ■); CON (control, □).
to rest (P ≤ 0.0001).
233

234
7.3.1.2 Heart rate
There were some differences for HR between groups at rest at baseline and this
remained constant across the duration of the study (all P ≤ 0.05; Figure 7.3). Resting
HR did not change across the duration of the study for all groups (P ≥ 0.05). A GROUP
x TIME interaction (P ≤ 0.01) was detected for peak-exercising HR, whereby HR
increased significantly from rest to peak-exercise for HL-T, LL-T, and BFR-C (Figure
7.2). However, the mean peak-exercising HR was significantly higher for HL-T in
comparison with both BFR-C and LL-T.

235
Figure 7.3 Heart rate responses
for all groups across the duration
of the training programme.
to rest (P ≤ 0.0001).
to all other trials (P ≤ 0.01).
to CON (P ≤ 0.05).
c indicates significant difference
to BFR-C (P ≤ 0.05).
d indicates significant difference
to HLRT (P ≤ 0.05).
235

236
7.3.1.3 Stroke volume
Resting SV was higher for CON in comparison with LL-T at all weeks (P ≤ 0.01), but
there were no other differences between groups (Figure 7.4). Resting SV did not change
across the duration of the study for all groups (P ≥ 0.05). A GROUP x TIME interaction
(P ≤ 0.05) was detected for peak-exercising SV, whereby SV decreased from rest to
peak-exercise for HL-T. However, there were no differences between groups at any
week for peak-exercise SV.

237
Figure 7.4 Stroke volume
responses for all groups across the
duration of the training
programme.
to rest (P ≤ 0.05).
to CON (P ≤ 0.05).
237

238
7.3.1.4 Blood pressures
There were no differences for systolic BP between groups at rest at baseline, and this
remained constant across the duration of the study (all P ≥ 0.05; Figure 7.5). In
addition, resting systolic BP did not change across the duration of the study for all
groups (P ≥ 0.05). A GROUP x TIME interaction (P ≤ 0.05) was detected for peak-
exercising systolic BP, whereby systolic BP increased significantly from rest to peak-
exercise for HL-T, LL-T, and BFR-C (Figure 7.5). However, the mean peak-exercising
systolic BP was significantly higher for HL-T in comparison with both BFR-C and LL-
T. When the peak-exercising data was grouped, systolic BP was decreased at week four
and eight in comparison with baseline (P ≤ 0.01). In addition, peak-exercising systolic
BP was decreased at week eight in comparison with week four.

239
Figure 7.5 Systolic blood pressure
responses for all groups across the
duration of the training
programme.
to rest (P ≤ 0.0001).
† indicates difference to week four
(P ≤ 0.05).
‡ indicates difference to week
eight (P ≤ 0.05).
to all other trials (P ≤ 0.05).
239

240
There were no differences for diastolic BP between groups at rest at baseline, and this
addition, resting diastolic BP did not change across the duration of the study for all
groups (P ≥ 0.05). A GROUP x TIME interaction (P ≤ 0.01) was detected for peak-
exercising diastolic BP, whereby diastolic BP increased significantly from rest to peak-
exercise for HL-T, LL-T, and BFR-C, but there were no differences between groups
(Figure 7.6).

241
Figure 7.6 Diastolic blood
pressure responses for all groups
across the duration of the training
programme.
to rest (P ≤ 0.0001).
241

242
There were no differences for MAP between groups at rest at baseline, and this
addition, resting MAP did not change across the duration of the study for all groups (P
≥ 0.05). A GROUP x TIME interaction (P ≤ 0.05) was detected for peak-exercising
MAP, whereby MAP increased significantly from rest to peak-exercise for HL-T, LL-T,
and BFR-C, but there were no differences between groups (Figure 7.7).

243
Figure 7.7 Mean arterial blood
pressure responses for all groups
across the duration of the training
programme.
to rest (P ≤ 0.0001).
243

244
7.3.1.5 Total peripheral resistance
There were no differences for resting or peak-exercising TPR between groups at
baseline, and this remained constant across the duration of the study (all P ≥ 0.05; Table
7.1). In addition, TPR did not change from rest to peak-exercise for all groups at
baseline, and this remained constant across the duration of the study (all P ≥ 0.05).
However, with the data normalized, there was a trend for peak-exercising TPR to be
higher at week 12 in comparison with baseline, but this was not significant (P = 0.076).
7.3.1.6 Rate pressure product
There were no differences for RPP between groups at rest at baseline, and this remained
constant across the duration of the study (all P ≥ 0.05; Table 7.1). In addition, resting
RPP did not change across the duration of the study for all groups (P ≥ 0.05). A
GROUP x TIME interaction (P ≤ 0.01) was detected for peak-exercising RPP, whereby
RPP increased significantly from rest to peak-exercise for HL-T, LL-T, and BFR-C. In
addition, peak-exercising RPP was higher for HL-T in comparison with both BFR-C
and LL-T, but there were no other differences between groups.

245
Table 7.1 Total peripheral resistance (TPR) and rate pressure product (RPP) responses expressed as a percentage change from rest. * indicates significant difference
to rest (P ≤ 0.05); a indicates significant difference to all other trials (P ≤ 0.01).
Total peripheral resistance
HL-T LL-T BFR-C CON
Rest Peak-exercise Rest Peak-exercise Rest Peak-exercise Rest Peak-exercise
Baseline 100 82 ± 13 100 84 ± 7 100 111 ± 8 100 -
Week 4 100 97 ± 5 100 99 ± 7 100 117 ± 18 100 -
Week 8 100 111 ± 14 100 86 ± 4 100 102 ± 9 100 -
Week 12 100 98 ± 12 100 87 ± 5 100 104 ± 7 100 -
Rate pressure product
HL-T LL-T BFR-C CON
Rest Peak-exercise Rest Peak-exercise Rest Peak-exercise Rest Peak-exercise
Baseline 100 286 ± 17*a
100 181 ± 13* 100 210 ± 16* 100 -
Week 4 100 255 ± 17*a
100 185 ± 12* 100 206 ± 12* 100 -
Week 8 100 251 ± 12*a
100 191 ± 13* 100 198 ± 13* 100 -
Week 12 100 252 ± 8*a
100 138 ± 14* 100 196 ± 14* 100 -
245

246
RPE was higher at baseline for HL-T and BFR-C in comparison with LL-T (P ≤ 0.05;
Figure 7.8). Following this, RPE significantly decreased for BFR-C at all weeks in
comparison with baseline, and was no longer different to LL-T (P ≤ 0.05). In addition,
while RPE decreased for HL-T at week 8 and week 12 in comparison with baseline,
RPE was still higher at all weeks in comparison with LL-T, but not BFR-C.
Figure 7.8 Rating of perceived exertion responses for all groups across the duration of the
training programme.
* indicates significant difference to baseline (P ≤ 0.05).
a indicates significant difference to BFR-C (P ≤ 0.05).
b denotes significant difference to HL-T (P ≤ 0.05).

247
Ratings of perceived pain were higher at baseline for HL-T and BFR-C in comparison
with LL-T (P ≤ 0.05; Figure 7.9). Following this, perceived pain significantly decreased
for HL-T and BFR-C at all weeks in comparison with baseline, but remained higher in
comparison with LL-T.
Figure 7.9 Rating of perceived pain responses for all groups across the duration of the training
programme.
* indicates significant difference to baseline (P ≤ 0.05).
a indicates significant difference to BFR-C (P ≤ 0.05).
b denotes significant difference to HL-T (P ≤ 0.05).

248
7.4 Discussion
The present study examined the acute haemodynamic and perceptual responses to BFR-
RT in comparison with more traditional resistance training techniques, while also
examining these responses over an eight week training and four week de-training
period. The major findings showed (i) peak-exercising HR, systolic BP, and RPP to be
significantly greater during HL-T in comparison with BFR-C and LL-T; (ii) no chronic
haemodynamic adaptations were observed at rest; (iii) peak-exercising systolic BP
decreased over the duration of the training programme, regardless of training group; and
(iv) overall, RPE and pain were higher for HL-T and BFR-C in comparison with LL-T,
however the perceptual responses decreased across the duration of the twelve week
study for both HL-T and BFR-C. These results in part support the hypothesis, and
suggest that while beneficial adaptations in muscle strength and mass may occur
following eight weeks of BFR-RT (see chapter six), this type of training was not
sufficient to produce significant adaptations in haemodynamic function in the current
study, but this was the same for all groups.
7.4.1 Acute haemodynamic responses during resistance exercise
One potential limitation of the current BFR-RE literature is that most lower-body
studies have only compared haemodynamic responses to load matched controls without
BFR. It was therefore interesting to note that while HL-T produced the greatest gains in
muscle strength and mass (see chapter six), the acute haemodynamic response, in
particular for HR, systolic BP, and RPP, were attenuated for BFR-C in comparison with
HL-T and similar to LL-T. Previous studies have shown that peak-exercising HR and
BP responses to HLRE can exceed the values seen in the current study, with one study
observing peak-exercise HR and BP responses reaching 170 bpm and 320/250 mmHg,

249
respectively, during lower-body resistance exercise (MacDougall et al., 1985). While
this was higher than the results seen in the current study for HL-T, most likely due to
allowing the Valsalva manoeuvre to be performed in the study by MacDougall et al.,
(1985) and different exercises performed (knee extension versus leg press), these results
highlight that HLRE induces significant increases in haemodynamic stress, which may
not be recommended for some clinical populations. In contrast, performing knee
extension exercise at 20% 1-RM with continuous BFR attenuated the peak-exercise HR,
systolic BP, and RPP responses in comparison with HL-T in the current study, a result
which is in agreement with previous lower-body BFR studies (Kacin and Strazar, 2011,
Takano et al., 2005). Therefore, the finding that BFR-RE attenuates the increase in
peak-exercise HR and BP responses to somewhere between HLRE and LLRE, while
still improving muscle function, may be important for special populations such as the
elderly or those with underlying cardiovascular diseases.
Traditionally it was thought that BFR-RE resulted in an acute reduction in SV due to a
decrease in venous return (Ozaki et al., 2010, Renzi et al., 2010, Takano et al., 2005).
Findings from the current study and chapter five did not reveal any significant change
in SV from rest to peak-exercise for BFR-C; however an acute decline in SV was seen
for HL-T in the current study. It is not known why these differences exist between the
current study and previous literature, but may be due to higher arbitrary pressures used
in previous studies (e.g. 160-180 mmHg for Takano et al., (2005) in comparison with
134 ± 4 mmHg in the current study), different exercise protocols (e.g. exercise to
muscular failure versus the standard 30/15/15/15 in the current study), or the use of
wide nylon cuffs in the current study in comparison to narrow elastic cuffs used
previously (Ozaki et al., 2010, Renzi et al., 2010, Takano et al., 2005). Furthermore, the
technique used for measuring SV in the current study was completed indirectly,

250
whereas seminal work by Takano et al., (2005) used real time beat-to-beat SV
measurements via impedance cardiography. Nevertheless, other studies have also
shown no acute change in SV during BFR-RE which supports results from the current
study (Downs et al., 2014). Therefore, in the absence of a change in SV observed in the
current study, it appears that the increase in peak-exercising Q̇ during BFR-C appears
largely driven by the increase in HR and TPR. In addition, the increase in peak-
exercising Q̇ may also have contributed to the increase in BP for all groups.
Overall, given the reduced acute haemodynamic stress observed during BFR-C in
comparison with HL-T, it appears that BFR-RE may be good alternative mode of
resistance exercise to HLRE with moderately equivalent training outcomes in muscular
function. While these results were observed in a young healthy untrained population, it
remains to be elucidated if a similar phenomenon occurs in special populations such as
the elderly and a variety of clinical populations that may already have underlying
cardiovascular and respiratory diseases, whereby this type of exercise/training may be
the most beneficial. Therefore, future studies should first examine the acute
haemodynamic responses to determine its safety and efficacy in these populations
before prescribing clinical patients to BFR-RT.
7.4.2 Chronic haemodynamic adaptations at rest and during exercise
Of particular interest to this study were the haemodynamic adaptations at rest and peak-
exercise following training and de-training. In line with the traditional HLRT literature
(Fleck, 1988, Hagberg et al., 1984, Katz and Wilson, 1992, Kelley and Kelley, 2000,
Lovell et al., 2009, Tsutsumi et al., 1997), it was expected that the completion of a full-
body resistance training program would induce reductions in resting HR and BP, and
similar adaptations may occur following BFR-RT. Results from the current study did

251
not support this hypothesis, whereby no change in any of the resting haemodynamic
measurements was observed for any group across the duration of the study. In
agreement, previous investigations have shown that resting HR does not decrease
following three (Kim et al., 2009) and four (Kacin and Strazar, 2011) weeks of BFR-
RT, while resting BP has been shown to decrease (Fahs et al., 2011a), increase (Kacin
and Strazar, 2011), or not change (Kim et al., 2009, Ozaki et al., 2012) in healthy
populations following BFR-RT. It is not known why there were no chronic adaptations
seen in the resting haemodynamic measurements for any of the groups in the current
study, considering the duration (eight weeks) and frequency (three training sessions per
week) of the training programme was expected to be sufficient to produce these
adaptations based on results from the HLRT literature (Fleck, 1988, Fleck, 1992).
However, it is possible that longer periods of training (i.e. ≥ 12 weeks) are required to
obtain these adaptations. In addition, it is probable that these adaptations were not
observed because the participants already had a low resting haemodynamic state at
baseline due to being a young and healthy population. For example, other BFR-RT
studies have used a similar cohort of participants as the current study and reported no
change in resting HR and BP, while evidence from short-term HLRT studies have been
reported as inconclusive in young normotensive individuals (Halbert et al., 1997).
Importantly though, there is some evidence that resting HR and BP can be reduced
following BFR-RT in older populations and/or those with cardiovascular disease. As an
example, a significant ~10% reduction in resting BP has been observed previously in
patients with metabolic syndrome (e.g. diagnosed clinical hypertension) (Satoh, 2011).
Alternatively, aerobic exercise (e.g. walking and cycling) either with or without BFR
has also been shown to induce favourable adaptations in resting haemodynamics in
older adults (Ozaki et al., 2011a, Ozaki et al., 2011b). Based on this information and
results from the current study, it appears that an eight week full-body BFR-RT

252
programme was not sufficient to induce reductions in resting HR and BP in a young
healthy population. Future studies should examine if these adaptations occur following
BFR-RT of longer durations (e.g. ≥ 12 weeks). In addition, as BFR-RT appears to be a
safe alternative to HLRT regarding acute haemodynamic responses while producing
moderately equivalent improvements in muscle strength and mass, future studies should
attempt to measure adaptations in resting haemodynamic function in clinical
populations such as the elderly and hypertensive individuals.
To the authors’ knowledge, only one study has previously examined the peak-
exercising adaptations in haemodynamics following BFR-RT. After the completion of
four weeks of resistance training of the knee extensors, no changes were observed in
peak-exercising HR or BP following LLRT or BFR-RT (Kacin and Strazar, 2011). In
the current study, it was observed that the group mean peak-exercising systolic BP
significantly decreased at week four (1.39% reduction) and eight (4.25% reduction) in
comparison with baseline. In addition, systolic BP continued to decrease from week
four to week eight; highlighting the need for longer training durations to induce this
adaptation. It is likely that the longer training duration per session (45 minutes versus
~10 minutes), length of training (24 versus 16 training sessions), and exercise selection
(multiple compound/single joint exercises versus single joint exercise) would account
for the differences between the current study and that of Kacin and Strazer (2011). In
contrast to the current BFR-RT literature, reductions in peak-exercising BP appears to
be a common adaptation observed following HLRT when exercising at the same
absolute load young healthy populations (Sale et al., 1994, Goldberg et al., 1994, Sale et
al., 1993), and evidence from the current study suggests these adaptations can be
induced following a full-body resistance training programme regardless of BFR, load,
or exercise volume.

253
One potential limitation to the current study was that other beneficial adaptations in
cardiovascular function may have occurred that were not detected. As an example,
BFR-RT of short-duration (≤ 6 weeks) has been shown to induce improvements in
vascular adaptations such increased calf microvascular filtration capacity (Evans et al.,
2010, Hunt et al., 2013), increased resting, peak-exercising, and post-exercise muscle
blood flow (Hunt et al., 2013, Patterson and Ferguson, 2010), and increased arterial
compliance (Fahs et al., 2013b). Furthermore, elevations in BP have been previously
associated with beneficial changes in arterial compliance following 10 weeks of BFR
walk training in the elderly (Ozaki et al., 2012). Indeed, it is possible that the reduction
in systolic BP was driven by peripheral adaptations rather than cardiac factors,
considering there was no change in Q̇ , HR, or SV. Therefore, while the current study
was unable to detect many changes in resting or peak-exercising haemodynamics for
BFR-C, it appears that other beneficial vascular adaptations may have occurred that
were undetected, and should therefore be considered in future studies.
Based on these results for resting and peak-exercising adaptations, while BFR-RT
seems effective at inducing gains in muscle strength and mass, the ability to induce
beneficial haemodynamic adaptations may be limited in young healthy populations.
Importantly, in combination with previous observations, the findings from the current
study suggest that BFR-RE does not appear to induce any adverse haemodynamic
responses when completed in a controlled manner by trained personnel. Therefore,
while BFR-RE should still be cautiously applied in clinical populations, particularly to
“high risk” individuals with underlying cardiovascular disease, the longer term benefits
of BFR-RT (i.e. increased muscle strength and mass) may outweigh the acute
haemodynamic stress.

254
7.4.1 Perceptual responses following resistance training
Initially, at baseline, RPE was higher for HL-T and BFR-C following knee extension
exercise, a finding that is consistent with previous literature for the lower-body
(Loenneke et al., 2010a, Wernbom et al., 2006, Wernbom et al., 2009, Fitschen et al.,
2013, Rossow et al., 2012) and the results from chapter five following upper-body
resistance exercise with BFR. A similar pattern was also detected for pain at baseline,
whereby pain was significantly higher for HL-T and BFR-C in comparison with LL-T.
This was similar to the findings by Hollander et al., (2010) who demonstrated BFR with
light-loads (30% 1-RM) increased pain similarly in comparison with traditional HLRE
(70% 1-RM). Overall, there is now a large body of evidence showing that an acute bout
of BFR-RE produces higher perceptual responses in exertion and pain in comparison
with load matched controls without BFR, at least when the resistance exercise protocol
is not performed until muscular failure. As mentioned previously (Loenneke et al.,
2010a, Wernbom et al., 2006), the increased perceptual response may limit the potential
use of BFR-RE in some clinical populations such as the elderly, or those completing
muscular rehabilitation programs following injury. However, perhaps the initial pain
and discomfort experienced by participants completing BFR-RE may be overcome by
continuing the resistance training program with BFR. Based on this hypothesis, the
long-term perceptual responses were also measured following four and eight weeks of
training.
For HL-T and BFR-C, both RPE and pain were reduced following four and eight weeks
of training in comparison with baseline. While pain was still significantly higher at
these time points for HL-T and BFR-C in comparison with LL-T, the reduction in RPE
for BFR-C meant that it was no longer different to LL-T, a finding which is in
agreement with previous literature (Fitschen et al., 2013). This suggests that regardless

255
of the intervention type, participants were able to adapt to the imposed exercise demand
and/or BFR stimulus. Single bouts of BFR-RE (Umbel et al., 2009, Wernbom et al.,
2012a, Iversen and Røstad, 2010, Thiebaud et al., 2013b) and HLRE (Chen and Nosaka,
2006) have been shown to induce muscle damage following exercise, but will likely
disappear following training, a phenomenon known as the ‘protective repeated bout
effect’ (Nosaka and Clarkson, 1995). The protective repeated bout effect has been
shown to last several weeks following multiple bouts of LLRE (Chen et al., 2010), and
up to six months following a single session of HLRE (Nosaka et al., 2001). It was
therefore interesting to note that RPE and pain remained lower at week 12 for HL-T and
BFR-C following the four week de-training period.
The mechanisms by which the body adapts via the repeated bout effect are unknown,
but are thought to occur via neural (e.g. increased motor unit recruitment), cellular (e.g.
blunted inflammatory response), and mechanical (e.g. increased muscle stiffness)
adaptations to damaging exercise (McHugh, 2003). While it was out of the scope of the
current study to measure the acute muscle damage responses, there is some evidence for
neural and cellular adaptations following BFR-RE that may be responsible for the
protective effect to muscle damage following training. As an example, an acute bout of
BFR-RE has been shown to recruit high threshold motor units similarly to HLRE
(Takarada et al., 2000c), while inflammatory markers such as interleukin-6 have been
shown to be attenuated for BFR-RE (Karabulut et al., 2013). In addition, heat-shock
proteins have been suggested to protect the muscle tissue from damage following
repeated bouts of resistance exercise (Koh, 2002). Heat shock proteins have been shown
to be elevated following damaging exercise of the elbow flexors (Thompson et al.,
2002), and also following an acute bout of BFR-RE (Cumming et al., 2014).
Furthermore, given that KE 1-RM strength was increased following training for BFR-C

256
and HL-T, it would seem plausible to suggest that the exercise simply became easier to
perform for the participants with regards to a reduced mechanical loading. Regardless
of the underlying mechanisms responsible for the protective effect following BFR-RT,
it is important to note that while an acute bout of continuous BFR during knee extension
exercise with 20% 1-RM resulted in similar perceptual responses as traditional HLRE,
when the exercise/training continued then RPE and pain decreased making it more
tolerable to complete. This finding may be particularly significant for practitioners such
as medical professionals, strength and conditioning coaches, and rehabilitation trainers
(e.g. physiotherapists) that may guide exercise prescription with clinical populations.

257
7.5 Conclusion
In conclusion, the present study showed that lower-body resistance exercise in
combination with continuous BFR demonstrates a limited rise in HR, systolic BP and
RPP to levels between those observed for HLRE and LLRE. However, despite some
increases in muscle strength and mass observed following a full-body BFR-RT program
(see chapter six), there were no beneficial adaptations observed in resting
haemodynamic responses following training. However, peak-exercising systolic BP
decreased across the duration of the training program, but this was the same for all
training groups. In addition, perceptual responses in RPE and pain decreased for BFR-C
following training, which suggests psychological improvements can also occur
following training, making the exercise bout more tolerable for the participant. Based
on the results from the current study, it is possible to suggest that if the purpose of
performing a resistance training program with BFR in young healthy adults is to
produce adaptations in resting and peak-exercising haemodynamics, then perhaps
longer training durations are required.

258
CHAPTER EIGHT:
General discussion

259
The primary aims of this thesis was to assess the efficacy of BFR resistance exercise
and training (BFR-RE/RT) on neuromuscular, haemodynamic, and perceptual
responses, as well as gaining a better understanding of the adaptations in muscle
strength and mass following a BFR-RT programme. The three experimental studies
undertaken for this thesis have produced several key and novel findings that contribute
to the traditional resistance training and BFR-RT literature.
Chapter four investigated the acute time-course response in corticomotor excitability
and intracortical inhibition following resistance exercise of the biceps brachii in
combination with BFR. While corticomotor excitability increased significantly for
light-load resistance exercise (LLRE), and high-pressure intermittent application of
BFR, the increase in MEP amplitude was highest for low-pressure continuous
application of BFR and remained so for up to 60 minutes post-exercise. Chapter five
investigated the acute time-course response in haemodynamic and perceptual variables
following the same resistance exercise protocols as chapter four. Results from this study
showed that LLRE of the biceps brachii in combination with low-pressure continuous
BFR demonstrated a limited rise in heart rate (HR), blood pressures (BP), cardiac
output (Q̇ ), rate pressure product (RPP), and perceptual responses to levels between
those observed for traditional heavy-load resistance exercise (HLRE) and LLRE.
From chapter four and five it was determined that in order to induce the greatest
modifications in corticomotor plasticity, as well as limiting the rise in haemodynamic
and perceptual responses, that low-pressure continuous application of BFR was a
preferable protocol in comparison with high-pressure intermittent BFR. Therefore, in
chapters six and seven, this BFR protocol was applied during a full-body resistance
training programme which consisted of eight weeks of training and a four-week de-
training period. Overall, muscle strength and mass increased similarly for low-pressure
continuous BFR and light-load resistance training (LLRT), while the increase following

260
heavy-load resistance training (HLRT) was greater. Similar to chapter four,
corticomotor excitability was increased significantly post-exercise for low-pressure
continuous BFR (30 min) and HLRT (60 min) following knee extension exercise, but
no chronic adaptations were observed in corticomotor plasticity for any group following
training. However, it cannot be ruled out that adaptations in spinal mechanisms or other
cortical structures also played a role at increasing muscle strength, but these currently
remain undetected. In addition, in chapter seven, while no beneficial adaptations were
observed in resting haemodynamic parameters following training, a reduction in peak-
exercising systolic BP was observed for all training groups at weeks four and eight in
comparison with baseline, but there were no other differences. When considering these
findings collectively, there are several overarching themes that warrant further
discussion that will be highlighted in the following sections.
8.1 Evidence of early corticomotor plasticity
Firstly, the findings from chapter four and chapter six provide some evidence for
corticomotor adaptations following both upper- and lower-body BFR-RE. In chapter
four, continuous low-pressure BFR during elbow flexion exercise at 20% 1-RM
produced a rapid and long lasting (up to 60 minutes) increase in corticomotor
excitability. This modification was greater in comparison with high-pressure
intermittent BFR as well as traditional heavy- and light-load resistance exercise.
Furthermore, in chapter six, continuous low-pressure BFR during knee extension
exercise at 20% 1-RM also produced a rapid and long lasting (up to 30 minutes)
increase in corticomotor excitability which was greater than a non-exercise control
condition. In both studies, no acute changes were observed for short-interval
intracortical inhibition (SICI) following resistance exercise with or without BFR,

261
suggesting that inhibitory circuits were not involved in the mechanisms responsible for
the net increase in corticomotor plasticity. Consistent with these results, cortical
inhibition has also been shown not to be acutely modified following ischemic nerve
deafferentation (Ziemann et al., 1998a) or under systemic hypoxic conditions (Rupp et
al., 2012). Based on these results, it appears that an acute bout of BFR-RE of both the
upper-body and lower-body affects the excitability of interneurons projecting onto
corticospinal cells that descend onto spinal motoneurons controlling the biceps brachii
and quadriceps. The most likely stimuli responsible for the acute modification in
corticomotor excitability arise from altered sensory function detected via group III and
IV muscle afferent fibres (Moritani et al., 1992, Karabulut et al., 2007, Yasuda et al.,
2010a). Early BFR-RE studies showed that muscle activity assessed via EMG was
significantly increased relative to LLRE, and similar to traditional HLRE (Takarada et
al., 2000c, Yasuda et al., 2006, Moritani et al., 1992, Yasuda et al., 2009). Group III and
IV muscle afferent fibres detect changes in tissue oxygen and carbon dioxide, hydrogen
ions, and metabolites such as lactate (Haouzi et al., 1999, Rotto and Kaufman, 1988),
all of which have been found to be modified during BFR-RE (Ganesan et al., 2014,
Yasuda et al., 2010a). It has been proposed that with the addition of the BFR pressure
and resultant occlusion of blood flow, the ischemic/hypoxic intramuscular environment
produced during BFR-RE may play a role in stimulating the increase in muscle
activation. Given that sensory feedback to cortical and/or subcortical areas during
exercise and under ischemic/hypoxic conditions has been proposed to alter muscle
activation and corticomotor excitability (Christie and Kamen, 2013, Gandevia et al.,
1996), evidence from the present thesis further supports a potential role of group III and
IV muscle afferents in modulating corticomotor excitability with BFR.

262
Given the finding of an acute increase in corticomotor excitability following an acute
bout of BFR-RE, chapter six also investigated the effect of corticomotor plasticity
following a training intervention. The results from chapter six were not able to provide
evidence of chronic adaptations in corticomotor plasticity reported via stimulus-
response curves following the resistance training programme, despite significant
increases in muscle strength in the absence of hypertrophy (at least at week four). This
finding was unexpected; as it was hypothesized that corticomotor plasticity would
increase, and this would account for the increase in strength following training, similar
to results found following traditional HLRT literature. Several HLRT studies have
observed increases in MEP amplitude at intensities above resting motor threshold
following resistance training interventions (Griffin and Cafarelli, 2007, Beck et al.,
2007, Hortobágyi et al., 2011, Leung et al., 2013, Weier and Kidgell, 2012). However,
these results are inconsistent, with others showing no change or even decreased MEP
amplitude post-training (Carroll et al., 2002, Jensen et al., 2005, Kidgell et al., 2010,
Latella et al., 2012). It has also been shown that the overall net excitability of the
corticospinal tract can be modulated via the release of cortical inhibition following
HLRT programmes (Weier et al., 2012, Latella et al., 2012), but again, a chronic
reduction in SICI following resistance training in chapter six was not evident.
Since a significant part of the corticospinal pathway is indirectly attached to the spinal
motoneuron pool via spinal interneuronal networks, the findings from this thesis cannot
exclude the contribution of functional changes that may have occurred at a segmental
level, particularly in chapter six whereby acute reductions in the maximal muscle
compound action potential (MMAX) were observed following HLRT. The results of this
thesis would support, in part, some form of adaptation within other cortical structures,
the brain stem, spinal cord circuits, and improvements in motor control/coordination,

263
given that no chronic changes were observed in corticomotor excitability and inhibition
using TMS. This would be consistent with recent HLRT studies that have demonstrated
increased neural drive from spinal motoneurons measured via surface EMG, H-reflex,
V-wave, CMEPs, and single motor unit recordings (Aagaard et al., 2002b, Del Balso
and Cafarelli, 2007, Fimland et al., 2009, Holtermann et al., 2007, Nuzzo et al., 2015).
As a primary aim of the current these was to make comparisons between BFR-RE/RT
and traditional modes of resistance exercise, it is important to discuss the corticomotor
responses for HLRE from chapters four and six herein. In chapter four there was no
change in MEP amplitude or SICI post-exercise following HLRE of the elbow flexors.
Given results from previous acute HLRE studies using TMS have shown acute
modulation in corticomotor plasticity, including increased excitability and/or reduced
inhibition (Leung et al., 2015, Nuzzo et al., 2015, Selvanayagam et al., 2011), this result
was unexpected. It was hypothesised that the resistance exercise protocol in chapter
four (four sets of 6-8 repetitions of elbow flexion exercise) somewhat limited the
centrally challenging nature of the exercise task, as participants were unable to maintain
the correct velocity of movement due to the heavy-load (80% 1-RM). Therefore, in
chapter six, the relative load was reduced to 70% 1-RM and the prescribed repetitions
increased to 8-10 repetitions per set whilst maintaining control of the velocity of the
movement via external pacing. Interestingly, MEP amplitude increased significantly for
up to 60 min following knee extension exercise for the HLRT group. This finding was
in agreement with recent studies that observed modifications in corticomotor plasticity
following HLRE tasks (Leung et al., 2015, Nuzzo et al., 2015). It is likely that the
increased number of repetitions performed in chapter six compared with chapter four
was responsible for this result, thereby increasing the centrally challenging nature of the
exercise bout. In addition, Leung et al. (2015) recently showed that an acute bout of

264
resistance exercise (70% 1-RM) increased corticomotor excitability and decreased SICI
post-exercise similar to visuomotor skill tasks, as long as the repetition timing was
controlled to an external audio cue (e.g. metronome). It is likely that sensory feedback
from contracting muscles, in particular group III and IV muscle afferents, were
responsible for the modification in use-dependant plasticity. In addition, the increase in
MEP amplitude post-exercise may reflect neuromuscular fatigue (Gandevia, 2001) for
the HLRT group whereby a reduction in MMAX was also observed post-exercise.
Furthermore, MVIC was reduced post-exercise when the data was grouped, therefore,
the effect of fatigue on the acute increase corticomotor excitability cannot be
completely ruled out.
8.2 Reduced haemodynamic response in the absence of chronic adaptations
The findings from chapter five and chapter seven demonstrated attenuated HR, BP, Q̇ ,
and RPP for low-pressure continuous BFR of the upper- and lower-body in comparison
with HLRE. As expected, the haemodynamic responses were lowest with LLRE, but in
some instances were similar to BFR-RE. Despite the comparison of all three modes of
resistance exercise being limited to approximately four studies in previous literature
with regards to haemodynamic function (Neto et al., 2014b, Downs et al., 2014, Poton
and Polito, 2014, Araújo et al., 2014), this effect was in agreement with results observed
previously in healthy young populations (Downs et al., 2014, Takano et al., 2005).
For traditional HLRT, increasing the exercise load/intensity and the amount of muscle
mass involved in the resistance exercise can significantly increase the haemodynamic
response to the exercise bout, particularly for HR and BP (MacDougall et al., 1985).
Although it was not an aim of the current thesis to make comparisons between different

265
resistance exercises with continuous BFR, it is interesting to note that during bilateral
knee extension exercise (chapter seven) most of the peak-exercising haemodynamic
responses observed were only slightly higher in comparison with unilateral elbow
flexion exercise (chapter five). This was despite a larger amount of muscle mass
involvement in chapter seven (quadriceps, bilateral) in comparison with chapter five
(biceps brachii, unilateral). To highlight this, it appeared that the peak-exercise response
during unilateral elbow flexion exercise versus bilateral knee extension was similar for
HR (106 ± 4 vs 114 ± 24 bpm, respectively), systolic BP (155 ± 7 vs 163 ± 9 mmHg,
respectively), diastolic BP (106 ± 6 vs 117 ± 4 mmHg, respectively), MAP (128 ± 5 vs
133 ± 6 mmHg, respectively), and Q̇ (6.21 ± 0.31 vs 7.64 ± 0.77 L.min-1
, respectively).
Both studies observed significant increases in these measures compared with resting
values, while the responses in HR, BP, and RPP for chapter five and chapter seven were
highest with HLRE in comparison with BFR-RE and LLRE. This result appears to
highlight that the inclusion of low-pressure continuous BFR to light-load (20% 1-RM)
resistance exercise may be a more preferential mode of training in comparison with
HLRT in order to reduce haemodynamic stress for both the lower- and upper-body.
However, the author acknowledges that a more complete range of exercises need to be
investigated in future to substantiate this claim. Overall, considering that BFR-RT has
been recommended as a potential alternative to HLRT for increasing muscle strength
and mass, the collective findings in chapter five and chapter seven regarding the acute
haemodynamic responses are particularly important for populations with already
increased contraindications to HLRE, such as the elderly, or those with cardiovascular,
respiratory, or metabolic diseases.
Given the attenuated responses in several of the acute haemodynamic variables
measured in chapter five and chapter seven for BFR-RE, it was hypothesized that eight

266
weeks of training would induce chronic adaptations in resting and peak-exercising
haemodynamics. However, findings from chapter seven revealed no adaptations in any
of the resting variables measured for all training groups following eight weeks of
resistance training. This finding was unexpected, given that previous full-body HLRT
studies have observed reductions in HR and BP following training (Fleck, 1988,
Hagberg et al., 1984, Katz and Wilson, 1992, Kelley and Kelley, 2000, Lovell et al.,
2009, Tsutsumi et al., 1997). However, in contrast, other HLRT studies have reported
no reductions in resting or peak-exercising haemodynamics (Sale et al., 1994, Goldberg
et al., 1994), with differences in exercise loads, volumes, and training durations and
frequencies making it difficult to make comparisons between studies. In addition,
several BFR studies have not reported reductions in resting HR (Kim et al., 2009, Kacin
and Strazar, 2011), while resting BP has been shown to decrease (Fahs et al., 2011a),
increase (Kacin and Strazar, 2011), or not change (Kim et al., 2009, Ozaki et al., 2012)
in healthy populations. It is likely that differences in BFR methodologies (i.e. final cuff
pressures, cuff width, and duration [intermittent vs continuous]) and resistance
exercise/training protocols (duration, frequency, single vs multi-joint) would account
for the variation in haemodynamic adaptations that have been previously observed in
comparison with the current study. As such, the results from chapter seven show
agreement with some sections of the BFR-RT literature.
Reductions in peak-exercising haemodynamics are also important, however, to the
authors’ knowledge only one study has previously examined these adaptations
following BFR-RT (Kacin and Strazar, 2011). Findings from chapter seven only
observed a reduction in peak-exercising systolic BP by 1.4% at week four and by 4.3%
by week eight. The decrease in systolic BP at week eight was greater than week four,
which highlights the need for longer resistance training programmes to induce this
adaptation. Given that the duration (eight weeks) and frequency (three training sessions

267
per week) of the resistance training programme appeared to be sufficient to induce
adaptations in resting and peak-exercising haemodynamics based on results from HLRT
literature (Fleck, 1988, Fleck, 1992), it is not known why beneficial adaptations in other
variables besides systolic BP were not observed. The most likely reason for this is that
the population examined in the current thesis already exhibited a low resting
haemodynamic state at baseline prior to training. While it was outside the scope of this
thesis, following BFR-RT of short durations (≤ 6 weeks), adaptations in peripheral
vascular responses have been observed previously in a similar cohort of participants as
the current study (Evans et al., 2010, Hunt et al., 2013, Patterson and Ferguson, 2010),
which may have remained undetected in the chapter seven. However, based on results
within this thesis, while BFR-RE attenuates the acute haemodynamic stress in
comparison with HLRE, if the goal of the resistance training programme is to induce
cardiovascular adaptations at rest or during exercise, then perhaps aerobic exercise
either with or without BFR would be more preferable.
8.3 Acute perceptual responses not such a limiting factor for training
The use of BFR-RE/RT has been recommended as a technique for those with limited
strength and functional capacities. However, the increased perceptual responses in
ratings of perceived exertion (RPE), pain, discomfort, delayed onset muscle soreness
(DOMS), and potential muscle damage have been viewed as a potential shortcoming for
its use in these populations (Loenneke et al., 2010a, Wernbom et al., 2006). In
agreement with previous studies, results from chapter five and seven demonstrated
increased RPE and pain following an acute bout of BFR-RE for the upper- and lower-
body, respectively.

268
It was particularly important to compare the perceptual responses for BFR-RE to more
traditional HLRE and LLRE. There is now a large body of evidence showing that BFR-
RE produces greater perceptual responses in RPE, pain, and discomfort in comparison
with load-matched controls without BFR (Hollander et al., 2010, Loenneke et al.,
2010a, Wernbom et al., 2006, Wernbom et al., 2009, Vieira et al., 2014, Fitschen et al.,
2013, Rossow et al., 2012). In agreement, results from chapter five and seven support
these findings, whereby both RPE and pain were greater for BFR-RE in comparison
with LLRE. In contrast to the LLRE data, less is known about the perceptual responses
for BFR-RE in comparison with HLRE (Vieira et al., 2014, Hollander et al., 2010,
Loenneke et al., 2015, Yasuda et al., 2010a). Previously, Hollander et al., (2010)
reported higher RPEs following continuous BFR-RE in comparison with HLRE of the
elbow flexors, while Yasuda et al., (2010a) reported higher responses for HLRE (18.7 ±
0.3) in comparison with both high-pressure (15.3 ± 0.2) and low-pressure BFR (14.6 ±
0.7). Additionally, it appears that if the exercise protocol is performed until muscle
failure, RPE and pain are higher for BFR-RE in comparison with HLRE (Vieira et al.,
2014, Loenneke et al., 2015). However, it may be difficult to compare these data with
the data from the present thesis as the resistance exercises employed, and BFR methods
used (final cuff pressure, duration of inflation, cuff width etc.) were different between
studies. This potentially limits the understanding of the perceptual responses to HLRE
and BFR-RE. Therefore, with the current evidence it is difficult to make any clear
recommendations. Considering that many favourable adaptations in muscle function
occur with BFR-RT similarly to HLRT, but with lighter-loads, then perhaps an exercise
protocol should be selected for BFR-RT as long as it does not induce perceptual
responses any greater than traditionally expected with HLRT.

269
Overall, and in agreement with Wernbom et al., (2006) and Loenneke et al., (2010a),
the combination of results from chapter five and seven regarding the increased
perceptual responses following BFR-RE suggests that this mode of exercise may be
limit its potential use in some clinical populations. As an extension on monitoring the
acute response to BFR-RE, the perceptual responses to an acute bout of knee extension
either with or without BFR across as 12 week training and de-training programme were
also examined in chapter seven. As mentioned above, RPE and pain were significantly
higher at baseline for BFR-C and HL-T in comparison with LL-T prior to beginning
resistance training. However, when the exercise stimulus was repeated over the duration
of the training programme, both RPE and pain decreased for BFR-C and HL-T, to a
point where RPE was no longer different for BFR-C in comparison with LL-T. This
finding was in agreement with previous BFR literature, however, the training related
perceptual responses is limited to only one previous study (Fitschen et al., 2013). Of
note, the decreased RPE and pain responses were also observed following four weeks of
de-training. Collectively, these results suggest that while an acute bout of BFR may
initially result in increased perceptual responses during exercise and delayed onset
muscle soreness for up to 48 hours post-exercise, if the resistance exercise is repeated
continuously as part of a training programme, the perceptual responses become
attenuated to a point where they are no longer different to load-matched controls
without BFR. Therefore, BFR-RE becomes more tolerable for participants to perform
with chronic use, perhaps indicating a more long-term protective response to muscle
damage following the initial exercise bout. Furthermore, it is likely that one of the
mechanisms responsible for the increased perceptual response is the combination of
high exercise volumes (sets x repetitions) as well as the additional BFR pressure
applied. Therefore, in order to minimise the perceptual responses during the initial
training phase with BFR, it might be recommended that lower training volumes should

270
be used, a method which has been shown to produce favourable increases in both
muscle strength and mass (Sakuraba and Ishikawa, 2009, Kim et al., 2009, Kim et al.,
2012b, Karabulut et al., 2010a, Karabulut et al., 2011a). Importantly as well, results
from this thesis highlight that the acute perceptual responses to a single resistance
training session with BFR may not be such a limiting factor with chronic use, as the
magnitude of the increase was no more than what would typically be expected for
traditional HLRE. This information may be important for practitioners when designing
resistance training and rehabilitation programmes using BFR.
8.4 Effects of resistance training on muscle strength and mass
One of the overarching aims of the current thesis was to examine the effects of BFR-RT
on muscle strength and mass, and compare these adaptations to more traditional HLRT
and LLRT. Since a seminal study conducted by Takarada et al., (2000c) found that the
gain in muscle strength and cross sectional area was similar for BFR-RT and HLRT,
with both greater than LLRT, it has been heavily cited throughout the literature that this
result is a common occurrence. Indeed, many studies since this time have shown similar
adaptations in muscle strength and mass between BFR-RT and HLRT (Karabulut et al.,
2010a, Karabulut et al., 2011a, Martín‐Hernández et al., 2013, Thiebaud et al., 2013a,
Karabulut et al., 2013, Lowery et al., 2013, Clark et al., 2010, Takarada et al., 2000c,
Kim et al., 2009, Laurentino et al., 2012). Additionally, there is a wealth of data
showing that BFR-RT produces more favourable gains in muscle strength, mass, and
endurance when compared with LLRT (Abe et al., 2005a, Abe et al., 2005b, Abe et al.,
2005c, Shinohara et al., 1998, Takarada et al., 2002, Takarada et al., 2000c, Takarada et
al., 2004, Yasuda et al., 2005, Yasuda et al., 2010b). Despite this, results from the
present thesis found that muscle strength and mass increased to different levels for all

271
training groups, depending on the resistance exercise and muscle group measured. For
example, knee extension 1-RM strength (the main outcome exercise) increased
similarly following eight weeks of BFR-RT (20.1%) and LLRT (13.4%), while the
magnitude of change was greater for HLRT (25.8%). However, leg lean mass (assessed
via DXA) was significantly increased by 2.3% following eight weeks of HLRT, and
quadriceps MTH was also increased for HLRT (14.4%) and LLRT (9.8%), but not
BFR-RT. Furthermore, resistance training of the upper-body had the greatest effect for
HLRT whereby there was a significant increase in bench press, seated row, and bicep
curl 1-RM strength. However, the between group differences were limited, with only
seated row 1-RM strength being greater for HLRT in comparison with all other groups.
In addition, while the increase in strength for most of the resistance exercises were
similar between training groups, it is important to note that these were typically greater
than a non-exercise control. Therefore, the results from chapter six as well as others
(Burgomaster et al., 2003, Yasuda et al., 2011, Yasuda et al., 2010c, Clark et al., 2010,
Karabulut et al., 2010a, Karabulut et al., 2011a, Karabulut et al., 2013) do not support
the notion that BFR-RT can induce greater increases in muscle strength and mass as
traditional HLRT, but appear to be more similar whilst also being greater than LLRT.
Because the ‘typical’ and hypothesized muscular adaptations were not observed
following BFR-RT, the specific BFR and resistance training protocols used within
chapter six should be examined further in order to explain the results from the current
thesis.
8.4.1 Method of blood flow restriction application
Results from chapter four and five showed that low-pressure (defined as less than
systolic BP) continuous BFR resulted in greater increases in corticomotor excitability

272
whilst reducing the haemodynamic and perceptual responses during elbow flexion
exercise at 20% 1-RM in comparison with high-pressure (defined as greater than
systolic BP) intermittent BFR. Based on these results, it was decided that low-pressure
continuous BFR would be utilized during the resistance training programme in chapter
six.
Even though the BFR pressure used during both lower-body and upper-body resistance
exercise in chapter six were still below systolic BP, the final exercise pressure was
equal to 60% of each individuals’ limb occlusion pressure (LOP). While the author is
unable to determine whether the selected pressure was sufficient enough to produce
largely beneficial adaptations to muscle strength and mass following training, this
percentage of restriction was within the 50-80% LOP as recommended recently by
Loenneke et al., (2014c). However, it is difficult to ascertain what the “optimal” BFR
pressure may be to induce improved muscular adaptations, and this “optimal” pressure
may be variable based on its use within different populations. Sumide et al., (2009)
observed significant increases in muscle strength and cross-sectional area with
pressures as low as 50 mmHg, while Counts et al., (2015) recently showed similar
adaptations in muscle strength following eight weeks of training with 40% and 90%
LOP with narrow cuffs (5 cm width). However, when performing resistance exercise
with light-loads (20% 1-RM) similar to the current study, Lixandrão et al., (2015)
showed that increasing the BFR pressure to 80% LOP (9.5 cm cuff width) resulted in a
greater increase in muscle mass compared with 40% LOP in young healthy populations
similar to participants in chapter six. Therefore, perhaps a greater relative BFR pressure
was required in the current thesis in order to induce greater changes in strength and
mass following training, and this would still fit within the recommendations by
Loenneke et al., (2014c).

273
Overall, a range of BFR pressures from 50-300 mmHg have been used in previous
literature to produce favourable muscular adaptations following short and longer term
training programs. Furthermore, it appears that both continuous and intermittent BFR
produce similar adaptations in strength and mass following training (Fitschen et al.,
2013). While it is difficult to compare these studies due to variations in BFR and
resistance training methodologies, overall, based on previous observations, the author is
confident that the BFR methodologies employed (i.e. final restriction pressure and
duration) within the current thesis were sufficient in order to significantly improve
muscle strength and mass following BFR-RT. While this was true for some exercises
and muscle groups measured, the magnitude of change between groups was not typical
of what has been observed previously. Therefore, the resistance training programme
employed within chapter six should also be questioned in order to better explain the
results.
8.4.2 Resistance training protocol
The majority of BFR literature has examined muscular adaptations following single-
joint/small muscle group (e.g. knee/elbow flexion/extension) training programmes.
However, some studies have measured muscular adaptations following body weight
circuit training (no external load) (Ishii et al., 2005), as well as multiple resistance
exercises for the upper- or lower-body (Kim et al., 2009, Loenneke et al., 2012g,
Karabulut et al., 2010a, Weatherholt et al., 2012, Thiebaud et al., 2013a). Therefore, a
novel aspect of chapter six was that, to the authors’ knowledge, this was the first study
to examine the effects of a full-body resistance training programme with BFR.

274
The involvement of multiple compound and isolation exercises included in the training
programme in chapter six is recommended by the American College of Sports Medicine
and other organisations (ACSM, 2013, Baechle and Earle, 2008) to maximise
adaptations in muscle strength and hypertrophy. When multiple resistance exercise have
been included in previous BFR-RT studies, the increase in muscle strength has been
found to be similar for BFR-RT and HLRT in young (Kim et al., 2009) and older
populations (Karabulut et al., 2010a). In addition, the increased volume with multiple
exercises has also been shown to produce similar adaptations in strength and cross
sectional area in comparison with LLRT (Weatherholt et al., 2012). Furthermore, when
the resistance training protocol utilizes repetitions to muscular failure, there are
typically no differences between BFR-RT and LLRT (Barcelos et al., 2015). Therefore,
the finding that BFR-RT resulted in similar muscular adaptations compared with LLRT
could perhaps be explained by the increased total volume of work (sets x repetitions)
completed, however, there does appear to be a volume threshold over which completing
more work is not beneficial (Martín‐Hernández et al., 2013, Barcelos et al., 2015).
Additionally, previous BFR-RT vs LLRT studies have mainly focussed on shorter
training durations (≤ 6 weeks) in comparison with eight weeks of training in chapter six.
There is some evidence to suggest that following longer training durations (≥ 8 weeks)
LLRT produces favourable gains in muscle strength and mass in young untrained
participants, regardless of the inclusion of BFR (Burgomaster et al., 2003, Weatherholt
et al., 2012, Barcelos et al., 2015, Moore et al., 2004). Therefore, the longer training
duration combined with increased training volume may in part explain the similar
results for BFR-RT and LLRT observed in the current thesis.

275
Finally, training loads equal to 20-30% 1-RM have typically been utilized during BFR-
RT to induce significant adaptations in muscle strength and mass (Loenneke et al.,
2011f, Abe et al., 2012). In chapter six, significant increases in 1-RM strength were
observed for BFR-RT which were greater than a non-exercise control, and similar to
LLRT and HLRT. Performing BFR-RT with 20% 1-RM has also been shown to be
sufficient to induce similar adaptations to HLRT (Karabulut et al., 2011a, Laurentino et
al., 2012). In contrast, it appears that other studies have utilized higher relative loads
equal to 30% (Clark et al., 2010), ~50% (Takarada et al., 2000c, Takarada et al., 2002),
and up to 70% (Cook et al., 2013) to produce similar or even greater adaptations
following BFR-RT in comparison with HLRT. In agreement, Lixandrão et al., (2015)
recently showed that higher loads (40% 1-RM) induced similar gains in cross sectional
area for the quadriceps but not 1-RM strength following five weeks of knee extension
training with BFR in comparison with HLRT (80% 1-RM). Therefore, it is probable
that if higher relative training loads (e.g. 40-50% 1-RM) were used in chapter six with a
healthy young population, greater increases in muscle strength and mass would have
occurred.
Of course, it is difficult to make comparisons between studies due to differences in BFR
methodologies (final cuff pressure, duration, cuff width), resistance training protocols
(load, volume, frequency, duration), and the population of interest (trained vs untrained,
young vs old). Therefore, such large discrepancies between studies make it difficult to
understand the real effect full-body BFR-RT may have in healthy young populations in
comparison with traditional HLRT. Overall, the results of this thesis support the use of
HLRT to develop muscle strength and mass in young healthy untrained individuals’.
However, it may be expected that for populations unable to lift heavy-loads (e.g. the
elderly, following musculoskeletal injury, or where muscle atrophy and weakness occur

276
due to the effects of inactivity or disease) that BFR-RT or indeed LLRT may be a more
preferential exercise modality, considering that some resistance exercises and muscle
groups increased similarly between training groups.
8.5 Limitations and future direction
There are limitations to this thesis that must be acknowledged and considered when
interpreting these findings, and several lines of future research can be identified to
further the studies presented.
Firstly, the present thesis examined neuromuscular, haemodynamic and perceptual
adaptations in healthy young untrained participants, and so limits the extrapolation to
other populations. If BFR-RT is to be recommended as an alternative to traditional
HLRT for clinical populations, future research is needed to determine the efficacy and
safety of its use in these populations. In addition, the results from this thesis may only
be representative of the BFR methodologies and resistance exercise/training
methodologies used, and may be difficult to extrapolate the data to different
combinations of BFR pressures, durations, and cuff widths, as well as resistance
exercises used. Therefore, future studies should examine these responses to other
exercises (resistance and aerobic), under different loads/intensities, using varying BFR
protocols, in order to determine the “optimal” exercise protocol, which will help with
the development of prescription guidelines for practitioners such as medical doctors,
strength and conditioning coaches and rehabilitation trainers (e.g. physiotherapists).
Results from chapter four and chapter six provide evidence of enhanced corticomotor
plasticity immediately following both upper-body and lower-body BFR-RE. While it
was hypothesised that the acute increase in corticomotor excitability was driven by

277
changes within the M1, the author cannot completely rule out other adaptations that
may have occurred in other cortical structures, the brain stem, spinal level or the lower
motoneuron pool. The increase in muscle strength observed for all training groups in
the absence of muscle hypertrophy could not be explained with the neuromuscular
measurements taken using TMS in chapter six. Therefore, future studies investigating
the neuromuscular adaptations to BFR-RE/RT should use TMS to measure changes in
intracortical facilitation (ICF), long-interval intracortical inhibition (LICI), and the
silent period duration. In addition, use of other techniques such as transcranial electrical
stimulation, H-reflex, V-wave, and CMEPs should be used simultaneously in order to
determine if the increase in strength observed following BFR-RT is due to
neuromuscular adaptations occurring elsewhere along the corticospinal tract that
currently remain undetected. When this body of work is undertaken, we will have a
much better understanding of the neuromuscular mechanisms involved in modulating
strength following BFR-RT.
Chapter five and chapter seven provide evidence of attenuated haemodynamic
responses during both upper-body and lower-body resistance exercise with low-pressure
continuous BFR in comparison with HLRE, which may prove to be a useful training
tool for clinical populations such as the elderly and those with some forms of
cardiovascular disease such as hypertension. In addition, chapter seven provides
evidence of reduced peak-exercising systolic BP following training, an important
adaptation to training, particularly for clinical populations. With limited available
evidence with regard to chronic reductions in cardiovascular measurements following
BFR-RT in clinical populations (Satoh, 2011), if BFR-RT is truly to be considered as a
potential alternative to HLRT then future studies should examine these responses in
elderly populations and in patients with cardiovascular and/or metabolic diseases.

278
8.6 Conclusion
The purpose of this thesis was to determine the efficacy of BFR-RE/RT on
neuromuscular, haemodynamic, and perceptual responses, as well as gaining a better
understanding of the mechanisms underlying adaptations in muscle strength and mass.
It was hypothesised that BFR-RE would induce greater modifications in corticomotor
plasticity while reducing the haemodynamic responses in comparison with LLRE. In
addition, BFR-RT would produce similar adaptations in corticomotor plasticity,
haemodynamics, as well as muscle strength and mass adaptations as traditional HLRT.
Chapter four and chapter six demonstrated that corticomotor excitability was increased
following an acute bout of resistance exercise with low-pressure continuous BFR of the
upper-body (biceps brachii) and lower-body (quadriceps), but no chronic adaptations
were seen in corticomotor plasticity following training of the knee extensors. In chapter
five and chapter seven it was demonstrated that an acute bout of low-pressure
continuous BFR of the upper-body (biceps brachii) and lower-body (quadriceps) limited
the rise in haemodynamic perceptual responses to levels between those observed for
HLRE and LLRE. However, there was no reduction in resting haemodynamics, and
only a reduction in peak-exercising systolic BP was observed following eight weeks of
training, regardless of intervention type (chapter seven). Finally, results from chapter
six demonstrate that in order to induce the greatest increase in maximal strength and
muscle mass, HLRT may still be the preferred method if an individual is able.
Nevertheless, LLRT either with or without BFR also produced significant increases in
both upper-body and lower-body muscle strength and mass and could be particularly
useful for populations that have limited resistance training capacities such as the
elderly, patients in early rehabilitation following injury, or where muscle atrophy and
weakness occur due to the effects of inactivity or disease. Collectively, the findings

279
from this thesis provide novel evidence that low-pressure continuous BFR in
combination with light-loads (20% 1-RM) has a beneficial effect on corticomotor
plasticity, haemodynamic function, and perceptual responses. In addition, maximal
strength and muscle mass were shown to increase following BFR-RT similarly to
HLRT and LLRT, and may be particularly useful when injury, disease, or motor
impairment prevents traditional HLRT.

281
AAGAARD, P., SIMONSEN, E. B., ANDERSEN, J. L., MAGNUSSON, P. &
DYHRE-POULSEN, P. 2002a. Increased rate of force development and neural
drive of human skeletal muscle following resistance training. Journal of Applied
Physiology, 93, 1318-26.
AAGAARD, P., SIMONSEN, E. B., ANDERSEN, J. L., MAGNUSSON, P. &
DYHRE-POULSEN, P. 2002b. Neural adaptation to resistance training: changes
in evoked V-wave and H-reflex responses. Journal of Applied Physiology, 92,
2309-18.
ABBRUZZESE, G., ASSINI, A., BUCCOLIERI, A., SCHIEPPATI, M. &
TROMPETTO, C. 1999. Comparison of intracortical inhibition and facilitation
in distal and proximal arm muscles in humans. The Journal of Physiology, 514,
895-903.
ABDELFATTAH, A. & SALEM, H. 2011. Effect of Occlusion Swimming Training on
Physiological Biomarkers and Swimming Performance. World, 4, 70-75.
ABE, T., BEEKLEY, M., HINATA, S., KOIZUMI, K. & SATO, Y. 2005a. Day-to-day
change in muscle strength and MRI-measured skeletal muscle size during 7 days
KAATSU resistance training: A case study. International Journal of KAATSU
Training Research, 1, 71-76.
ABE, T., DEHOYOS, D. V., POLLOCK, M. L. & GARZARELLA, L. 2000. Time
course for strength and muscle thickness changes following upper and lower
body resistance training in men and women. European Journal of Applied
ABE, T., KAWAMOTO, K., YASUDA, T., KEARNS, C., MIDORIKAWA, T. &
SATO, Y. 2005b. Eight days KAATSU-resistance training improved sprint but
not jump performance in collegiate male track and field athletes. International
Journal of KAATSU Training Research, 1, 19-23.
ABE, T., KEARNS, C., FUJITA, S., SAKAMAKI, M., SATO, Y. & BRECHUE, W.
2009. Skeletal muscle size and strength are increased following walk training
with restricted leg muscle blood flow: implications for training duration and
frequency. International Journal of KAATSU Training Research, 5, 9-15.
ABE, T., KEARNS, C. & SATO, Y. 2006. Muscle size and strength are increased
following walk training with restricted venous blood flow from the leg muscle,
Kaatsu-walk training. Journal of Applied Physiology, 100, 1460.
ABE, T., KONDO, M., KAWAKAMI, Y. & FUKUNAGA, T. 1994. Prediction
equations for body composition of Japanese adults by B‐mode ultrasound.
American Aournal of Human Biology, 6, 161-170.
ABE, T., LOENNEKE, J. P., FAHS, C. A., ROSSOW, L. M., THIEBAUD, R. S. &
BEMBEN, M. G. 2012. Exercise intensity and muscle hypertrophy in blood
flow restricted limbs and non-restricted muscles: a brief review. Clinical
Physiology and Functional Imaging.
ABE, T., SAKAMAKI, M., FUJITA, S., OZAKI, H., SUGAYA, M., SATO, Y. &
NAKAJIMA, T. 2010. Effects of Low-Intensity Walk Training With Restricted
Leg Blood Flow on Muscle Strength and Aerobic Capacity in Older Adults.
Journal of Geriatric Physical Therapy, 33, 34.
ABE, T., YASUDA, T., MIDORIKAWA, T., SATO, Y., KEARNS, C., INOUE, K.,
KOIZUMI, K. & ISHII, N. 2005c. Skeletal muscle size and circulating IGF-1
are increased after two weeks of twice daily ìKAATSUî resistance training.
International Journal of KAATSU Training Research, 1, 6-12.
ANAND, S. & HOTSON, J. 2002. Transcranial magnetic stimulation:
neurophysiological applications and safety. Brain Cogn, 50, 366-86.
ANDERSEN, L. L., ANDERSEN, J. L., MAGNUSSON, S. P. & AAGAARD, P. 2005.
Neuromuscular adaptations to detraining following resistance training in

282
previously untrained subjects. European Journal of Applied Physiology, 93,
511-518.
ARAÚJO, J. P., SILVA, E. D., SILVA, J. C., SOUZA, T. S., LIMA, E. O., GUERRA,
I. & SOUSA, M. S. 2014. The Acute Effect of Resistance Exercise with Blood
Flow Restriction with Hemodynamic Variables on Hypertensive Subjects.
Journal of Human Kinetics, 43, 79-85.
ARMSTRONG, R. B. 1984. Mechanisms of exercise-induced delayed onset muscular
soreness: a brief review. Medicine and Science in Sports and Exercise, 16, 529.
BAECHLE, T. R. & EARLE, R. W. 2008. Essentials of Strength Training and
Conditioning, Human Kinetics Publishers.
BARCELOS, L. C., NUNES, P. R. P., DE SOUZA, L. R. M. F., DE OLIVEIRA, A. A.,
FURLANETTO, R., MAROCOLO, M. & ORSATTI, F. L. 2015. Low-load
resistance training promotes muscular adaptation regardless of vascular
occlusion, load, or volume. European Journal of Applied Physiology, 1-10.
BARKER, A., JALINOUS, R. & FREESTON, I. 1985. Non-invasive magnetic
stimulation of human motor cortex. Lancet, 1, 1106 - 1107.
BECK, S., TAUBE, W., GRUBER, M., AMTAGE, F., GOLLHOFER, A. &
SCHUBERT, M. 2007. Task-specific changes in motor evoked potentials of
lower limb muscles after different training interventions. Experimental Brain
Research, 1179, 51-60.
BEEKLEY, M., SATO, Y. & ABE, T. 2005. KAATSU-walk training increases serum
bone-specific alkaline phosphatase in young men. International Journal of
KAATSU Training Research, 1, 77-81.
BELL, C. 2008. Cardiovascular Physiology in exercise and sport, Churchill
Livingstone.
BENWELL, N. M., SACCO, P., HAMMOND, G. R., BYRNES, M. L., MASTAGLIA,
F. L. & THICKBROOM, G. W. 2006. Short-interval cortical inhibition and
corticomotor excitability with fatiguing hand exercise: a central adaptation to
fatigue? Experimental Brain Research, 170, 191-198.
BIRD, S. P., TARPENNING, K. M. & MARINO, F. E. 2005. Designing resistance
training programmes to enhance muscular fitness: a review of the acute
programme variables. Sports Medicine, 35, 841-851.
BORG, G. 1982. Psychophysical bases of perceived exertion. Medicine & Science in
Sports & Exercise, 14, 377.
BORG, G. 1998. Borg's perceived exertion and pain scales, Human Kinetics
Publishers.
BOTTARO, M., MARTINS, B., GENTIL, P. & WAGNER, D. 2009. Effects of rest
duration between sets of resistance training on acute hormonal responses in
trained women. Journal of Science and Medicine in Sport, 12, 73-78.
BRASIL-NETO, J. P., PASCUAL-LEONE, A., VALLS-SOLÉ, J., CAMMAROTA,
A., COHEN, L. G. & HALLETT, M. 1993a. Postexercise depression of motor
evoked potentials: a measure of central nervous system fatigue. Experimental
Brain Research, 93, 181-184.
BRASIL-NETO, J. P., VALLS-SOLVR, J., PASCUAL-LEONE, A., CAMMAROTA,
A., AMASSIAN, V. E., CRACCO, R., MACCABEE, P., CRACCO, J.,
HALLETT, M. & COHEN, L. G. 1993b. Rapid modulation of human cortical
motor outputs following ischaemic nerve block. Brain, 116, 511.
BROWN, S., BYRD, R., JAYASINGHE, M. & JONES, D. 1983. Echocardiographic
characteristics of competitive and recreational weight lifters. Journal of
Cardiovascular Ultrasonography, 2, 163-165.
BURGOMASTER, K., MOORE, D., SCHOFIELD, L., PHILLIPS, S., SALE, D. &
GIBALA, M. 2003. Resistance training with vascular occlusion: metabolic

283
adaptations in human muscle. Medicine & Science in Sports & Exercise, 35,
1203.
BYRNE, H. K. & WILMORE, J. H. 2000. The Effects of Resistance Training on
Resting Blood Pressure in Women. The Journal of Strength & Conditioning
Research, 14, 411-418.
CAMPOS, G. E., LUECKE, T. J., WENDELN, H. K., TOMA, K., HAGERMAN, F.
C., MURRAY, T. F., RAGG, K. E., RATAMESS, N. A., KRAEMER, W. J. &
STARON, R. S. 2002. Muscular adaptations in response to three different
resistance-training regimens: specificity of repetition maximum training zones.
European Journal of Applied Physiology, 88, 50-60.
CARROLL, T., BARTON, J., HSU, M. & LEE, M. 2009. The effect of strength
training on the force of twitches evoked by corticospinal stimulation in humans.
Acta Physiologica, 197, 161-173.
CARROLL, T. J., LEE, M., HSU, M. & SAYDE, J. 2008. Unilateral practice of a
ballistic movement causes bilateral increases in performance and corticospinal
excitability. Journal of Applied Physiology, 104, 1656-1664.
CARROLL, T. J., RIEK, S. & CARSON, R. G. 2001. Neural adaptations to resistance
training: implications for movement control. Sports Medicine, 31, 829-40.
CARROLL, T. J., RIEK, S. & CARSON, R. G. 2002. The sites of neural adaptation
induced by resistance training in humans. Journal of Physiology, 544, 641-652.
CARROLL, T. J., SELVANAYAGAM, V., RIEK, S. & SEMMLER, J. 2011. Neural
adaptations to strength training: moving beyond transcranial magnetic
stimulation and reflex studies. Acta Physiologica, 202, 119-140.
CARTEE, G. D., DOUEN, A. G., RAMLAL, T., KLIP, A. & HOLLOSZY, J. 1991.
Stimulation of glucose transport in skeletal muscle by hypoxia. Journal of
Applied Physiology, 70, 1593-1600.
CARTER, J. B., BANISTER, E. W. & BLABER, A. P. 2003a. Effect of endurance
exercise on autonomic control of heart rate. Sports Medicine, 33, 33-46.
CARTER, J. R., RAY, C. A., DOWNS, E. M. & COOKE, W. H. 2003b. Strength
training reduces arterial blood pressure but not sympathetic neural activity in
young normotensive subjects. Journal of Applied Physiology, 94, 2212-2216.
CARTER, R., WATENPAUGH, D. E., WASMUND, W. L., WASMUND, S. L. &
SMITH, M. L. 1999. Muscle pump and central command during recovery from
exercise in humans. Journal of Applied Physiology, 87, 1463-1469.
CHAPMAN, J. P., CHAPMAN, L. J. & ALLEN, J. J. 1987. The measurement of foot
preference. Neuropsychologia, 25, 579-584.
CHEN, R., CROS, D., CURRA, A., DI LAZZARO, V., LEFAUCHEUR, J. P.,
MAGISTRIS, M. R., MILLS, K., R√∂SLER, K. M., TRIGGS, W. J. &
UGAWA, Y. 2008. The clinical diagnostic utility of transcranial magnetic
stimulation: report of an IFCN committee. Clinical Neurophysiology, 119, 504-
532.
CHEN, T. C., CHEN, H.-L., LIN, M.-J., WU, C.-J. & NOSAKA, K. 2010. Potent
protective effect conferred by four bouts of low-intensity eccentric exercise.
Medicine Science in Sports & Exercise, 42, 1004-1012.
CHEN, T. C. & NOSAKA, K. 2006. Responses of elbow flexors to two strenuous
eccentric exercise bouts separated by three days. Journal of Strength &
Conditioning Research, 20, 108-116.
CHEUNG, K., HUME, P. A. & MAXWELL, L. 2003. Delayed onset muscle soreness:
treatment strategies and performance factors. Sports Medicine, 33, 145-164.
CHIPCHASE, L., SCHABRUN, S., COHEN, L., HODGES, P., RIDDING, M.,
ROTHWELL, J., TAYLOR, J. & ZIEMANN, U. 2012. A checklist for assessing
the methodological quality of studies using transcranial magnetic stimulation to

284
study the motor system: An international consensus study. Clinical
Neurophysiology.
CHIU, D., WANG, H. H. & BLUMENTHAL, M. R. 1976. Creatine phosphokinase
release as a measure of tourniquet effect on skeletal muscle. Archives of
Surgery, 111, 71-74.
CHRISTIE, A. & KAMEN, G. 2013. Cortical inhibition is reduced following short-
term training in young and older adults. AGE, 1-10.
CLARK, B., MANINI, T., HOFFMAN, R., WILLIAMS, P., GUILER, M., KNUTSON,
M., MCGLYNN, M. & KUSHNICK, M. 2010. Relative safety of 4 weeks of
blood flow restricted resistance exercise in young, healthy adults. Scandinavian
Journal of Medicine & Science in Sports.
CLARKSON, P. M., NOSAKA, K. & BRAUN, B. 1992. Muscle function after
exercise-induced muscle damage and rapid adaptation. Medicine and Science in
Sports and Exercise, 24, 512.
CLASSEN, J., LIEPERT, J., WISE, S. P., HALLETT, M. & COHEN, L. G. 1998.
Rapid plasticity of human cortical movement representation induced by practice.
Journal of Neurophysiology, 79, 1117.
CONNOLLY, D. A. J., SAYERS, S. P. & MCHUGH, M. P. 2003. Treatment and
prevention of delayed onset muscle soreness. Journal of Strength and
COOK, C. J., KILDUFF, L. P. & BEAVEN, C. M. 2013. Three Weeks of Occlusion
Training Can Improve Strength and Power in Trained Athletes. International
Journal of Sports Physiology and Performance.
COOK, S., CLARK, B. & PLOUTZ-SNYDER, L. 2007. Effects of exercise load and
blood-flow restriction on skeletal muscle function. Medicine & Science in Sports
& Exercise, 39, 1708.
COOK, S. B., BROWN, K. A., DERUISSEAU, K., KANALEY, J. A. & PLOUTZ-
SNYDER, L. L. 2010. Skeletal muscle adaptations following blood flow-
restricted training during 30 days of muscular unloading. Journal of Applied
COOK, S. B., KANALEY, J. A. & PLOUTZ-SNYDER, L. L. 2014. Neuromuscular
function following muscular unloading and blood flow restricted exercise.
European Journal of Applied Physiology, 1-9.
CORVINO, R. B., OLIVEIRA, M. F. M. D., SANTOS, R. P. D., DENADAI, B. S. &
CAPUTO, F. 2014. Four weeks of blood flow restricted training increases time
to exhaustion at severe intensity cycling exercise. Revista Brasileira de
Cineantropometria & Desempenho Humano, 16(5), 570-578.
COUNTS, B. R., DANKEL, S. J., BARNETT, B. E., KIM, D., MOUSER, J. G.,
ALLEN, K. M., THIEBAUD, R. S., ABE, T., BEMBEN, M. G. &
LOENNEKE, J. P. 2015. The influence of relative blood flow restriction
pressure on muscle activation and muscle adaptation. Muscle & Nerve.
CRENSHAW, A. G., HARGENS, A. R., GERSHUNI, D. H. & RYDEVIK, B. R. 1988.
Wide tourniquet cuffs more effective at lower inflation pressures. Acta
Orthopaedica, 59, 447-451.
CUMMING, K. T., PAULSEN, G., WERNBOM, M., UGELSTAD, I. & RAASTAD,
T. 2014. Acute response and subcellular movement of HSP27, αB-crystallin and
HSP70 in human skeletal muscle after blood flow restricted low-load resistance
exercise. Acta Physiologica, 211(4), 634-646.
CURRA, A., MODUGNO, N., INGHILLERI, M., MANFREDI, M., HALLETT, M. &
BERARDELLI, A. 2002. Transcranial magnetic stimulation techniques in
clinical investigation. Neurology, 59, 1851-9.

285
DARLING, W. G., WOLF, S. L. & BUTLER, A. J. 2006. Variability of motor
potentials evoked by transcranial magnetic stimulation depends on muscle
activation. Experimental Brain Research, 174, 376-85.
DE SOUSA, N. M., MAGOSSO, R. F., DIPP, T., PLENTZ, R. D., MARSON, R. A.,
MONTAGNOLLI, A. N., MARTINS, R. A., PEREZ, S. E. & BALDISSERA,
V. 2014. Continuous blood pressure response at different intensities in leg press
exercise. European Journal of Preventive Cardiology, 21, 1324-1331.
DEL BALSO, C. & CAFARELLI, E. 2007. Adaptations in the activation of human
skeletal muscle induced by short-term isometric resistance training. Journal of
DHAMU, H., MALLIARAS, P., TWYCROSS-LEWIS, R. & MAFFULLI, N. 2012. A
systematic review of resting left ventricular systolic and diastolic function and
adaptation in elite weightlifters. British Medical Bulletin, 104, 129-141.
DICKHUTH, H., SIMON, G., KINDERMANN, W., WILDBERG, A. & KEUL, J.
1979. Echocardiographic studies on athletes of various sport-types and non-
athletic persons. Zeitschrift fur Kardiologie, 68, 449-453.
DOWNS, M. E., HACKNEY, K. J., MARTIN, D., CAINE, T. L., CUNNINGHAM, D.,
O’CONNOR, D. P. & PLOUTZ-SNYDER, L. 2014. Acute Vascular and
Cardiovascular Responses to Blood Flow-Restricted Exercise. Medicine &
Science in Sports & Exercise.
DUCHATEAU, J. & ENOKA, R. M. 2002. Neural adaptations with chronic activity
patterns in able-bodied humans. American Journal of Physical Medical
Rehabilitation, 81, S17-27.
DUQUE, J., MAZZOCCHIO, R., STEFAN, K., HUMMEL, F., OLIVIER, E. &
COHEN, L. G. 2008. Memory formation in the motor cortex ipsilateral to a
training hand. Cerebral Cortex, 18, 1395-1406.
ELLEFSEN, S., HAMMARSTRÖM, D., STRAND, T. A., ZACHAROFF, E., WHIST,
J. E., RAUK, I., NYGAARD, H., VEGGE, G., HANESTADHAUGEN, M. &
WERNBOM, M. 2015. Blood flow-restricted strength training displays high
functional and biological efficacy in women: a within-subject comparison with
high-load strength training. American Journal of Physiology-Regulatory,
Integrative and Comparative Physiology, ajpregu. 00497.2014.
ENOKA, R. 1997. Neural adaptations with chronic physical activity. Journal of
Biomechanics, 30, 447-455.
ENOKA, R. & FUGLEVAND, A. 2001. Motor unit physiology: some unresolved
issues. Muscle & Nerve, 24, 4-17.
ESBJORNSSON, M., JANSSON, E., SUNDBERG, C., SYLVEN, C., EIKEN, O.,
NYGREN, A. & KAIJSER, L. 1993. Muscle fibre types and enzyme activities
after training with local leg ischaemia in man. Acta Physiologica Scandinavica,
148, 233-242.
EVANS, C., VANCE, S. & BROWN, M. 2010. Short-term resistance training with
blood flow restriction enhances microvascular filtration capacity of human calf
muscles. Journal of Sports Sciences, 28, 999-1007.
FAHS, C. A., LOENNEKE, J. P., ROSSOW, L. M. & BEMBEN, M. G. 2013a. Cross-
over muscular adaptation to blood flow-restricted exercise. Medicine Science in
Sports and Exercise, 45, 1018.
FAHS, C. A., LOENNEKE, J. P., ROSSOW, L. M., THIEBAUD, R. S. & BEMBEN,
M. G. 2012. Methodological considerations for blood flow restricted resistance
exercise. Journal of Trainology, 1, 14-22.
FAHS, C. A., ROSSOW, L. M., LOENNEKE, J. P., THIEBAUD, R. S., KIM, D.,
BEMBEN, D. A. & BEMBEN, M. G. 2011a. Effect of different types of lower

286
body resistance training on arterial compliance and calf blood flow. Clinical
FAHS, C. A., ROSSOW, L. M., SEO, D. I., LOENNEKE, J. P., SHERK, V. D., KIM,
E., BEMBEN, D. A. & BEMBEN, M. G. 2011b. Effect of different types of
resistance exercise on arterial compliance and calf blood flow. European
Journal of Applied Physiology, 1-7.
FAHS, C. A., ROSSOW, L. M., THIEBAUD, R. S., LOENNEKE, J. P., KIM, D.,
ABE, T., BECK, T. W., FEEBACK, D. L., BEMBEN, D. A. & BEMBEN, M.
G. 2013b. Vascular adaptations to low-load resistance training with and without
blood flow restriction. European Journal of Applied Physiology, 1-10.
FALES, J. T., HEISEY, S. R. & ZIERLER, K. L. 1962. Blood flow from and oxygen
uptake by muscle, during and after partial venous occlusion. The American
Journal of Physiology, 203, 470.
FARINA, D., MERLETTI, R. & ENOKA, R. M. 2004. The extraction of neural
strategies from the surface EMG. Journal of Applied Physiology, 96, 1486.
FARUP, J., PAOLI, F., BJERG, K., RIIS, S., RINGGARD, S. & VISSING, K. 2015.
Blood flow restricted and traditional resistance training performed to fatigue
produce equal muscle hypertrophy. Scandinavian Journal of Medicine &
Science in Sports.
FIMLAND, M., HELGERUD, J., GRUBER, M., LEIVSETH, G. & HOFF, J. 2009.
Functional maximal strength training induces neural transfer to single-joint
tasks. European Journal of Applied Physiology, 107, 21-29.
FISHER, M. M. 2001. The effect of resistance exercise on recovery blood pressure in
normotensive and borderline hypertensive women. Journal of Strength and
FITSCHEN, P., KISTLER, B., JEONG, J., CHUNG, H., WU, P., WALSH, M. &
WILUND, K. 2013. Perceptual effects and efficacy of intermittent or continuous
blood flow restriction resistance training. Clinical Physiology and Functional
Imaging.
FLECK, S. J. 1988. Cardiovascular adaptations to resistance training. Medicine &
Science in Sports & Exercise, 20, S146.
FLECK, S. J. 1992. Cardiovascular responses to strength training. Strength and power
in Sport, 387-406.
FLECK, S. J. & DEAN, L. S. 1987. Resistance-training experience and the pressor
response during resistance exercise. Journal of Applied Physiology, 63, 116-120.
FLECK, S. J. & KRAEMER, W. 2014. Designing Resistance Training Programs, 4E,
Human Kinetics.
FLECK, S. J. & KRAEMER, W. J. 1988. Resistance Training: Basic Principles (Part 1
of 4). Physician and Sports Medicine, 16.
FOLLAND, J. P. & WILLIAMS, A. G. 2007. The adaptations to strength training:
morphological and neurological contributions to increased strength. Sports
Medicine, 37, 145-168.
FONTANA, P., BOUTELLIER, U. & TOIGO, M. 2010. Non-invasive haemodynamic
assessments using Innocor™ during standard graded exercise tests. European
Journal of Applied Physiology, 108, 573-580.
FRY, C. S., GLYNN, E. L., DRUMMOND, M. J., TIMMERMAN, K. L., FUJITA, S.,
ABE, T., DHANANI, S., VOLPI, E. & RASMUSSEN, B. B. 2010. Blood flow
restriction exercise stimulates mTORC1 signaling and muscle protein synthesis
in older men. Journal of Applied Physiology, 108, 1199.
FUJITA, S., ABE, T., DRUMMOND, M. J., CADENAS, J. G., DREYER, H. C.,
SATO, Y., VOLPI, E. & RASMUSSEN, B. B. 2007. Blood flow restriction

287
during low-intensity resistance exercise increases S6K1 phosphorylation and
muscle protein synthesis. Journal of Applied Physiology, 103, 903.
FUJITA, S., MIKESKY, A., SATO, Y. & ABE, T. 2008a. Fatigue Characteristics
during Maximal Concentric Leg Extension Exercise with Blood Flow
Restriction. International Journal of KAATSU Training Research, 3, 27-31.
FUJITA, T., BRECHUE, W., KURITA, K., SATO, Y. & ABE, T. 2008b. Increased
muscle volume and strength following six days of low-intensity resistance
training with restricted muscle blood flow. International Journal of KAATSU
Training Research, 4, 1-8.
GANDEVIA, S. 2001. Spinal and supraspinal factors in human muscle fatigue.
Physiological Reviews, 81, 1725-1789.
GANDEVIA, S., ALLEN, G. M., BUTLER, J. E. & TAYLOR, J. L. 1996. Supraspinal
factors in human muscle fatigue: evidence for suboptimal output from the motor
cortex. The Journal of Physiology, 490, 529-536.
GANESAN, G., COTTER, J. A., REULAND, W., CERUSSI, A. E., TROMBERG, B.
J. & GALASSETTI, P. 2014. Effect of Blood Flow Restriction on Tissue
Oxygenation during Knee Extension. Medicine Science in Sports and Exercise.
GAVIN, T., DREW, J., KUBIK, C., POFAHL, W. & HICKNER, R. 2007. Acute
resistance exercise increases skeletal muscle angiogenic growth factor
expression. Acta Physiologica, 191, 139-146.
GIACOBBE, V., VOLPE, B. T., THICKBROOM, G. W., FREGNI, F., PASCUAL-
LEONE, A., KREBS, H. I. & EDWARDS, D. J. 2011. Reversal of TMS-
induced motor twitch by training is associated with a reduction in excitability of
the antagonist muscle. Journal of Neuroengineering and Rehabilitation, 8, 46.
GJOVAAG, T., HJELMELAND, A., ØYGARD, J., VIKNE, H. & MIRTAHERI, P.
2015. Resistance exercise and acute blood pressure responses. The Journal of
Sports Medicine and Physical Fitness.
GODFREY, R., MADGWICK, Z. & WHYTE, G. 2003. The exercise-induced growth
hormone response in athletes. Sports Medicine, 33, 599-613.
GOLDBERG, L., ELLIOT, D. L. & KUEHL, K. S. 1994. A comparison of the
cardiovascular effects of running and weight training. The Journal of Strength &
GOLDFARB, A., GARTEN, R., CHEE, P., CHO, C., REEVES, G., HOLLANDER, D.,
THOMAS, C., ABOUDEHEN, K., FRANCOIS, M. & KRAEMER, R. 2008.
Resistance exercise effects on blood glutathione status and plasma protein
carbonyls: influence of partial vascular occlusion. European Journal of Applied
GOODALL, S., TWOMEY, R. & AMANN, M. 2014. Acute and chronic hypoxia:
implications for cerebral function and exercise tolerance. Fatigue: Biomedicine,
Health & Behavior, 2, 73-92.
GOODWILL, A. M., PEARCE, A. J. & KIDGELL, D. J. 2012. Corticomotor plasticity
following unilateral strength training. Muscle & Nerve.
GORDON, N. F. 2009. ACSM's guidelines for exercise testing and prescription,
Lippincott Williams & Wilkins.
GOTSHALL, R., GOOTMAN, J., BYRNES, W., FLECK, S. & VALOVICH, T. 1999.
Noninvasive characterization of the blood pressure response to the double-leg
press exercise. JEPonline, 2.
GRAHAM, B., BREAULT, M. J., MCEWEN, J. A. & MCGRAW, R. W. 1993.
Occlusion of arterial flow in the extremities at subsystolic pressures through the
use of wide tourniquet cuffs. Clinical Orthopaedics and Related Research, 286,
257.

288
GRIFFIN, L. & CAFARELLI, E. 2005. Resistance training: cortical, spinal, and motor
unit adaptations. Canadian Journal of Applied Physiology, 30, 328-340.
GRIFFIN, L. & CAFARELLI, E. 2007. Transcranial magnetic stimulation during
resistance training of the tibialis anterior muscle. J Electromyography and
Kinesiology, 17, 446-52.
GUALANO, B., NEVES JR, M., LIMA, F. R., PINTO, A., LAURENTINO, G.,
BORGES, C., BAPTISTA, L., ARTIOLI, G. G., AOKI, M. S. & MORISCOT,
A. 2010a. Resistance training with vascular occlusion in inclusion body
myositis: a case study. Medicine Science in Sports and Exercise, 42, 250-254.
GUALANO, B., UGRINOWITSCH, C., NEVES JR, M., LIMA, F., PINTO, A.,
LAURENTINO, G., TRICOLI, V., LANCHA JR, A. & ROSCHEL, H. 2010b.
Vascular Occlusion Training for Inclusion Body Myositis: A Novel Therapeutic
Approach. Journal of Visualized Experiments.
GUSTAFSSON, T., PUNTSCHART, A., KAIJSER, L., JANSSON, E. &
SUNDBERG, C. J. 1999. Exercise-induced expression of angiogenesis-related
transcription and growth factors in human skeletal muscle. American Journal of
Physiology-Heart and Circulatory Physiology, 276, H679-H685.
HACKNEY, K.J., EVERETT, M., SCOTT, J.M., PLOUTZ-SNYDER, L. 2012. Blood
flow-restricted exercise in space. Extreme Physiology & Medicine, 1(1):12.
HAGBERG, J. M., EHSANI, A. A., GOLDRING, D., HERNANDEZ, A., SINACORE,
D. R. & HOLLOSZY, J. O. 1984. Effect of weight training on blood pressure
and hemodynamics in hypertensive adolescents. The Journal of Pediatrics, 104,
147-151.
HAGBERG, J. M., MONTAIN, S. J. & MARTIN, W. H. 1987. Blood pressure and
hemodynamic responses after exercise in older hypertensives. Journal of
HAKKINEN, K., ALEN, M., KALLINEN, M., NEWTON, R. & KRAEMER, W. 2000.
Neuromuscular adaptation during prolonged strength training, detraining and re-
strength-training in middle-aged and elderly people. European Journal of
HAKKINEN, K., KOMI, P., ALEN, M. & KAUHANEN, H. 1987. EMG, muscle fibre
and force production characteristics during a 1 year training period in elite
weight-lifters. European Journal of Applied Physiology and Cccupational
HALBERT, J. A., SILAGY, C. A., FINUCANE, P., WITHERS, R., HAMDORF, P. &
ANDREWS, G. 1997. The effectiveness of exercise training in lowering blood
pressure: a meta-analysis of randomised controlled trials of 4 weeks or longer.
Journal of Human Hypertension, 11, 641-649.
HALLETT, M. 2000. Transcranial magnetic stimulation and the human brain. Nature,
406, 147-150.
HALLETT, M. 2007. Transcranial magnetic stimulation: a primer. Neuron, 55, 187 -
199.
HANNUM, S. & KASCH, F. 1981. Acute postexercise blood pressure response of
hypertensive and normotensive men. Scandinavian. Journal of Sports Science,
3, 11-15.
HAOUZI, P., HILL, J. M., LEWIS, B. K. & KAUFMAN, M. P. 1999. Responses of
group III and IV muscle afferents to distension of the peripheral vascular bed.
Journal of Applied Physiology, 87, 545-553.
HASKELL, W. L., LEE, I.-M., PATE, R. R., POWELL, K. E., BLAIR, S. N.,
FRANKLIN, B. A., MACERA, C. A., HEATH, G. W., THOMPSON, P. D. &
BAUMAN, A. 2007. Physical activity and public health: updated

289
recommendation for adults from the American College of Sports Medicine and
the American Heart Association. Circulation, 116, 1081.
HASLAM, D. R. S., MCCARTNEY, N., MCKELVIE, R. S. & MACDOUGALL, J. D.
1988. Direct measurements of arterial blood pressure during formal
weightlifting in cardiac patients. Journal of Cardiopulmonary Rehabilitation
and Prevention, 8, 213.
HENDY, A. M. & KIDGELL, D. J. 2013. Anodal tDCS applied during strength
training enhances motor cortical plasticity. Medicine and Science in Sports and
Exercise, 45, 1721-1729.
HENDY, A. M., SPITTLE, M. & KIDGELL, D. J. 2011. Cross education and
immobilisation: Mechanisms and implications for injury rehabilitation. Journal
of Science and Medicine in Sport.
HENNEMAN, E., SOMJEN, G. & CARPENTER, D. O. 1965. Functional significance
of cell size in spinal motoneurons. Journal of Neurophysiology, 28, 560.
HOLLANDER, D. B., REEVES, G. V., CLAVIER, J. D., FRANCOIS, M. R.,
THOMAS, C. & KRAEMER, R. R. 2010. Partial Occlusion During Resistance
Exercise Alters Effort Sense and Pain. The Journal of Strength & Conditioning
Research, 24, 235.
HOLTERMANN, A., ROELEVELD, K., ENGSTROM, M. & SAND, T. 2007.
Enhanced H-reflex with resistance training is related to increased rate of force
development. European Journal of Applied Physiology.
HORIUCHI, M. & OKITA, K. 2012. Blood Flow Restricted Exercise and Vascular
Function. International Journal of Vascular Medicine, 2012.
HORTOBÁGYI, T., RICHARDSON, S. P., LOMAREV, M., SHAMIM, E.,
MEUNIER, S., RUSSMAN, H., DANG, N. & HALLETT, M. 2009. Chronic
low-frequency rTMS of primary motor cortex diminishes exercise training-
induced gains in maximal voluntary force in humans. Journal of Applied
HORTOBÁGYI, T., RICHARDSON, S. P., LOMAREV, M., SHAMIM, E.,
MEUNIER, S., RUSSMAN, H., DANG, N. & HALLETT, M. 2011.
Interhemispheric plasticity in humans. Medicine and Science in Sports and
Exercise, 43, 1188-1199.
HORTOBYAGI, T., LAMBERT, N. J. & HILL, J. P. 1997. Greater cross education
following training with muscle lengthening than shortening. Medicine & Science
in Sports & Exercise, 29, 107.
HUNT, J. E., GALEA, D., TUFFT, G., BUNCE, D. & FERGUSON, R. A. 2013. Time
course of regional vascular adaptations to low load resistance training with
blood flow restriction. Journal of Applied Physiology.
IIDA, H., KURANO, M., TAKANO, H., KUBOTA, N., MORITA, T., MEGURO, K.,
SATO, Y., ABE, T., YAMAZAKI, Y. & UNO, K. 2007. Hemodynamic and
neurohumoral responses to the restriction of femoral blood flow by KAATSU in
healthy subjects. European Journal of Applied Physiology, 100, 275-285.
IIDA, H., KURANO, M., TAKANO, H., OONUMA, H., IMUTA, H., KUBOTA, N.,
MORITA, T., MEGURO, K., SATO, Y. & ABE, T. 2006. Can KAATSU be
used for an orthostatic stress in astronauts?: A case study. International Journal
of KAATSU Training Research, 2, 45-52.
ISHII, N., MADARAME, H., ODAGIRI, K., NAGANUMA, M. & SHINODA, K.
2005. Circuit training without external load induces hypertrophy in lower-limb
muscles when combined with moderate venous occlusion. International Journal
of KAATSU Training Research, 1, 24-28.
ITEM, F., DENKINGER, J., FONTANA, P., WEBER, M., BOUTELLIER, U. &
TOIGO, M. 2011. Combined Effects of Whole-Body Vibration, Resistance

290
Exercise, and Vascular Occlusion on Skeletal Muscle and Performance.
International Journal of Sports Medicine.
IVERSEN, E. & RØSTAD, V. 2010. Low-load ischemic exercise-induced
rhabdomyolysis. Clinical Journal of Sport Medicine, 20, 218.
JACOBS, K. M. & DONOGHUE, J. P. 1991. Reshaping the cortical motor map by
unmasking latent intracortical connections. Science, 251, 944-7.
JAKOVLJEVIC, D. G., NUNAN, D., DONOVAN, G., HODGES, L. D.,
SANDERCOCK, G. R. H. & BRODIE, D. A. 2008. Comparison of cardiac
output determined by different rebreathing methods at rest and at peak exercise.
European Journal of Applied Physiology, 102, 593-599.
JAMES, E. G. & KARABULUT, M. 2013. Vascular restriction decreases EMG
regularity during walking. Human Movement Science, 32, 389-399.
JENSEN, J. L., MARSTRAND, P. C. & NIELSEN, J. B. 2005. Motor skill training and
strength training are associated with different plastic changes in the central
nervous system. Journal of Applied Physiology, 99, 1558-68.
KACIN, A. & STRAZAR, K. 2011. Frequent low load ischemic resistance exercise to
failure enhances muscle oxygen delivery and endurance capacity. Scandinavian
KAIJSER, L., SUNDBERG, C. J., EIKEN, O., NYGREN, A., ESBJORNSSON, M.,
SYLVEN, C. & JANSSON, E. 1990. Muscle oxidative capacity and work
performance after training under local leg ischemia. Journal of Applied
KAMEN, G. 2004a. Neural issues in the control of muscular strength. Research
Quarterly for Exercise and Sport, 75, 3-8.
KAMEN, G. 2004b. Reliability of motor-evoked potentials during resting and active
contraction conditions. Medicine and Science in Sports and Exercise, 36, 1574-
1579.
KAMEN, G. & KNIGHT, C. A. 2004. Training-related adaptations in motor unit
discharge rate in young and older adults. Journals of Gerontology and
Biological Science and Medical Science, 59, 1334-8.
KANDEL, E. R., SCHWARTZ, J. H., JESSELL, T. M., SIEGELBAUM, S. A. &
HUDSPETH, A. 1991. Principles of Neural Science, Elsevier New York.
KARABULUT, M., ABE, T., SATO, Y. & BEMBEN, M. 2007. Overview of
neuromuscular adaptations of skeletal muscle to KAATSU Training.
KARABULUT, M., ABE, T., SATO, Y. & BEMBEN, M. G. 2010a. The effects of
low-intensity resistance training with vascular restriction on leg muscle strength
in older men. European Journal of Applied Physiology, 108, 147-155.
KARABULUT, M., BEMBEN, D. A., SHERK, V. D., ANDERSON, M. A., ABE, T. &
BEMBEN, M. G. 2011a. Effects of high-intensity resistance training and low-
intensity resistance training with vascular restriction on bone markers in older
men. European Journal of Applied Physiology, 111, 1659-1667.
KARABULUT, M., CRAMER, J. T., ABE, T., SATO, Y. & BEMBEN, M. G. 2010b.
Neuromuscular fatigue following low-intensity dynamic exercise with externally
applied vascular restriction. Journal of Electromyography and Kinesiology, 20,
440-447.
KARABULUT, M., MCCARRON, J., ABE, T., SATO, Y. & BEMBEN, M. 2011b.
The effects of different initial restrictive pressures used to reduce blood flow
and thigh composition on tissue oxygenation of the quadriceps. Journal of
Sports Sciences, 29, 951-958.

291
KARABULUT, M. & PEREZ, G. 2013. Neuromuscular Response to Varying Pressures
Created by Tightness of Restriction Cuff. Journal of Electromyography and
Kinesiology.
KARABULUT, M., SHERK, V. D., BEMBEN, D. A. & BEMBEN, M. G. 2013.
Inflammation marker, damage marker and anabolic hormone responses to
resistance training with vascular restriction in older males. Clinical Physiology
and Functional Imaging.
KATZ, J. & WILSON, B. 1992. The effects of a six-week, low-intensity Nautilus
circuit training program on resting blood pressure in females. The Journal of
Sports Medicine and Physical Fitness, 32, 299.
KAWADA, S. & ISHII, N. 2005. Skeletal muscle hypertrophy after chronic restriction
of venous blood flow in rats. Medicine & Science in Sports & Exercise, 37,
1144.
KELLEY, G. A. & KELLEY, K. S. 2000. Progressive resistance exercise and resting
blood pressure: a meta-analysis of randomized controlled trials. Hypertension,
35, 838-843.
KENNEY, M. J. & SEALS, D. R. 1993. Postexercise hypotension. Key features,
mechanisms, and clinical significance. Hypertension, 22, 653-664.
KERR, A., SLATER, G. J., BYRNE, N. & NANA, A. 2015. Reliability of 2 Different
Positioning Protocols for Dual-Energy X-ray Absorptiometry Measurement of
Body Composition in Healthy Adults. Journal of Clinical Densitometry.
KIDGELL, D. J. & PEARCE, A. J. 2009. Neural adaptations following cross-education
strength training: A pilot study. Journal of Science and Medicine in Sport, 12,
52-53.
KIDGELL, D. J. & PEARCE, A. J. 2010. Corticospinal properties following short-term
strength training of an intrinsic hand muscle. Human Movement Science, In
Press, Corrected Proof.
KIDGELL, D. J. & PEARCE, A. J. 2011. What has transcranial magnetic stimulation
taught us About neural adaptations To strength training? A brief review. The
Journal of Strength & Conditioning Research.
KIDGELL, D. J., STOKES, M. A., CASTRICUM, T. J. & PEARCE, A. J. 2010.
Neurophysiological responses after short-term strength training of the biceps
brachii muscle. The Journal of Strength & Conditioning Research, 24, 3123.
KIERS, L., CROS, D., CHIAPPA, K. H. & FANG, J. 1993. Variability of motor
potentials evoked by transcranial magnetic stimulation. Electroencephalography
and Clinical Neurophysiology/Evoked Potentials Section, 89, 415-423.
KIM, D., SINGH, H., YOUNG, K., FAHS, C. A., ROSSOW, L. M., LOENNEKE, J.
P., THIEBAUD, R. S., KIM, E., SHERK, K. & YE, X. Effects Of Low Intensity
Cycling With Blood Flow Restriction On Body Composition, Strength, And
Vo2max. 2012a. Medicine and Science in Sports and Exercise, 361-362.
KIM, S., SHERK, V., BEMBEN, M. & BEMBEN, D. 2009. Effects of short-term, low-
intensity resistance training with vascular restriction on arterial compliance in
untrained young men. International Journal of KAATSU Training Research, 5,
1-8.
KIM, S., SHERK, V. D., BEMBEN, M. G. & BEMBEN, D. A. 2012b. Effects of Short
Term Low Intensity Resistance Training with Blood Flow Restriction on Bone
Markers and Muscle Cross-Sectional Area in Young Men. International Journal
of Exercise Science, 5.
KOBAYASHI, M. & PASCUAL-LEONE, A. 2003. Transcranial magnetic stimulation
in neurology. Lancet Neurol, 2, 145-56.
KOH, T. J. 2002. Do small heat shock proteins protect skeletal muscle from injury?
Exercise and Sport Sciences Reviews, 30, 117-121.

292
KORTHUIS, R. J., GRANGER, D. N., TOWNSLEY, M. I. & TAYLOR, A. E. 1985.
The role of oxygen-derived free radicals in ischemia-induced increases in canine
skeletal muscle vascular permeability. Circulation Research, 57, 599-609.
KRAEMER, W., ADAMS, K., CAFARELLI, E., DUDLEY, G., DOOLY, C.,
FEIGENBAUM, M., FLECK, S., FRANKLIN, B., FRY, A. & HOFFMAN, J.
2002. American College of Sports Medicine. American College of Sports
Medicine position stand. Progression models in resistance training for healthy
adults. Medicine and Science in Sports and Exercise, 34, 364-380.
KRAEMER, W. & RATAMESS, N. 2004. Fundamentals of resistance training:
progression and exercise prescription. Medicine & Science in Sports & Exercise,
36, 674.
KRAEMER, W. J., MARCHITELLI, L., GORDON, S. E., HARMAN, E., DZIADOS,
J. E., MELLO, R., FRYKMAN, P., MCCURRY, D. & FLECK, S. J. 1990.
Hormonal and growth factor responses to heavy resistance exercise protocols.
Journal of Applied Physiology, 69, 1442.
KRILEY, L. 2014. Effects of a Seven-Week Practical Blood Flow Restriction Traing
Program on Lower-Body Strength and Power. Doctoral Dissertation.
KUBO, K., KOMURO, T., ISHIGURO, N., TSUNODA, N., SATO, Y., ISHII, N.,
KANEHISA, H. & FUKUNAGA, T. 2006. Effects of low-load resistance
training with vascular occlusion on the mechanical properties of muscle and
tendon. Journal of Applied Biomechanics, 22, 112.
KUBOTA, A., SAKURABA, K., KOH, S., OGURA, Y. & TAMURA, Y. 2010. Blood
flow restriction by low compressive force prevents disuse muscular weakness.
Journal of Science and Medicine in Sport.
KUBOTA, A., SAKURABA, K., SAWAKI, K., SUMIDE, T. & TAMURA, Y. 2008a.
Prevention of disuse muscular weakness by restriction of blood flow. Medicine
& Science in Sports & Exercise, 40, 529.
KUBOTA, N., TAKANO, H., TSUTSUMI, T., KURANO, M., IIDA, H., YASUDA,
T., MEGURO, K., MORITA, T., SATO, Y. & KAWASHIMA, S. 2008b.
Resistance exercise combined with KAATSU during simulated weightlessness.
LACKMY, A. & MARCHAND-PAUVERT, V. 2010. The estimation of short intra-
cortical inhibition depends on the proportion of spinal motoneurones activated
by corticospinal inputs. Clinical Neurophysiology, 121, 612-621.
LAMOTTE, M., NISET, G. & BORNE, P. 2005. The effect of different intensity
modalities of resistance training on beat-to-beat blood pressure in cardiac
patients. Journal of Cardiovascular Risk, 12, 12.
LARSSON, J. & HULTMAN, E. 1979. The effect of long-term arterial occlusion on
energy metabolism of the human quadriceps muscle. Scandinavian Journal of
Clinical and Laboratory Investigation, 39, 257-264.
LATELLA, C., KIDGELL, D. J. & PEARCE, A. J. 2012. Reduction in corticospinal
inhibition in the trained and untrained limb following unilateral leg strength
training. European Journal of Applied Physiology, 112, 3097-3107.
LAURENTINO, G., UGRINOWITSCH, C., AIHARA, A., FERNANDES, A.,
PARCELL, A., RICARD, M. & TRICOLI, V. 2008. Effects of strength training
and vascular occlusion. International Journal of Sports Medicine, 29, 664-667.
LAURENTINO, G. C., UGRINOWITSCH, C., ROSCHEL, H., AOKI, M. S.,
SOARES, A. G., NEVES JR, M., AIHARA, A. Y., DA ROCHA CORREA
FERNANDES, A. & TRICOLI, V. 2012. Strength training with blood flow
restriction diminishes myostatin gene expression. Medicine & Science in Sports
& Exercise, 44, 406.

293
LAVENDER, A. P. & NOSAKA, K. 2008. A light load eccentric exercise confers
protection against a subsequent bout of more demanding eccentric exercise.
Journal of Science and Medicine in Sport, 11, 291-298.
LEE, M., GANDEVIA, S. C. & CARROLL, T. 2009. Short-term strength training does
not change cortical voluntary activation. Medicine and Science in Sports and
Exercise, 41, 1452-1460.
LEE, S.-J. 2004. Regulation of muscle mass by myostatin. Annual Review of Cell and
Developmental Biology, 20, 61-86.
LEMMER, J. T., HURLBUT, D. E., MARTEL, G. F., TRACY, B. L., IVEY, F. M.,
METTER, E. J., FOZARD, J. L., FLEG, J. L. & HURLEY, B. F. 2000. Age and
gender responses to strength training and detraining. Medicine and Science in
Sports and Exercise, 32, 1505-1512.
LENTINI, A. C., MCKELVIE, R. S., MCCARTNEY, N., TOMLINSON, C. W. &
MACDOUGALL, J. D. 1993. Left ventricular response in healthy young men
during heavy-intensity weight-lifting exercise. Journal of Applied Physiology,
75, 2703-2710.
LENTZ, M. & NIELSEN, J. F. 2002. Post-exercise facilitation and depression of M
wave and motor evoked potentials in healthy subjects. Clinical
Neurophysiology, 113, 1092-1098.
LEONARD, C. T., KANE, J., PERDAEMS, J., FRANK, C., GRAETZER, D. G. &
MORITANI, T. 1994. Neural modulation of muscle contractile properties
during fatigue: afferent feedback dependence. Electroencephalography and
Clinical Neurophysiology/Evoked Potentials Section, 93, 209-217.
LEUNG, M., RANTALAINEN, T., TEO, W.-P. & KIDGELL, D. 2015. Motor Cortex
excitability is not differentially modulated following skill and strength training.
Neuroscience.
LEUNG, M., SPITTLE, M. & KIDGELL, D. J. 2013. Corticospinal Excitability
Following Short-Term Motor Imagery Training of a Strength Task. Journal of
Imagery Research in Sport and Physical Activity, 8, 35-44.
LINNAMO, V., PAKARINEN, A., KOMI, P. V., KRAEMER, W. J. & H‰KKINEN,
K. 2005. Acute hormonal responses to submaximal and maximal heavy
resistance and explosive exercises in men and women. The Journal of Strength
& Conditioning Research, 19, 566.
LIXANDRÃO, M. E., UGRINOWITSCH, C., LAURENTINO, G., LIBARDI, C. A.,
AIHARA, A. Y., CARDOSO, F. N., TRICOLI, V. & ROSCHEL, H. 2015.
Effects of exercise intensity and occlusion pressure after 12 weeks of resistance
training with blood-flow restriction. European Journal of Applied Physiology, 1-
10.
LJUBISAVLJEVIĆ, M., MILANOVIĆ, S., RADOVANOVIĆ, S., VUKČEVIĆ, I.,
KOSTIĆ, V. & ANASTASIJEVIĆ, R. 1996. Central changes in muscle fatigue
during sustained submaximal isometric voluntary contraction as revealed by
transcranial magnetic stimulation. Electroencephalography and Clinical
Neurophysiology/Electromyography and Motor Control, 101, 281-288.
LOENNEKE, J., BALAPUR, A., THROWER, A., BARNES, J. & PUJOL, T. 2010a.
The Perceptual Responses to Occluded Exercise. International Journal of Sports
Medicine.
LOENNEKE, J., FAHS, C., ROSSOW, L., ABE, T. & BEMBEN, M. 2011a. The
anabolic benefits of venous blood flow restriction training may be induced by
muscle cell swelling. Medical Hypotheses.
LOENNEKE, J., THIEBAUD, R. & ABE, T. 2014a. Does blood flow restriction result
in skeletal muscle damage? A critical review of available evidence.
Scandinavian Journal of Medicine & Science in Sports.

294
LOENNEKE, J., THIEBAUD, R., ABE, T. & BEMBEN, M. 2014b. Blood Flow
Restriction Pressure Recommendations: The Hormesis Hypothesis. Medical
Hypotheses.
LOENNEKE, J., WILSON, J., WILSON, G., PUJOL, T. & BEMBEN, M. 2011b.
Potential safety issues with blood flow restriction training. Scandinavian
LOENNEKE, J. P., ABE, T., WILSON, J., THIEBAUD, R., FAHS, C., ROSSOW, L.
& BEMBEN, M. 2012a. Blood flow restriction: An evidence based progressive
model (Review). Acta Physiologica Hungarica, 99, 235-250.
LOENNEKE, J. P., ALLEN, K. M., MOUSER, J. G., THIEBAUD, R. S., KIM, D.,
ABE, T. & BEMBEN, M. G. 2014c. Blood flow restriction in the upper and
lower limbs is predicted by limb circumference and systolic blood pressure.
LOENNEKE, J. P., FAHS, C., THIEBAUD, R., ROSSOW, L., ABE, T., YE, X., KIM,
D. & BEMBEN, M. 2012b. The acute muscle swelling effects of blood flow
restriction. Acta Physiologica Hungarica, 99, 400-410.
LOENNEKE, J. P., FAHS, C. A., ROSSOW, L. M., SHERK, V. D., THIEBAUD, R.
S., ABE, T., BEMBEN, D. A. & BEMBEN, M. G. 2011c. Effects of cuff width
on arterial occlusion: implications for blood flow restricted exercise. European
LOENNEKE, J. P., FAHS, C. A., ROSSOW, L. M., THIEBAUD, R. S., MATTOCKS,
K. T., ABE, T. & BEMBEN, M. G. 2013a. Blood Flow Restriction Pressure
Recommendations: A Tale of Two Cuffs. Frontiers in Physiology, 4.
LOENNEKE, J. P., FAHS, C. A., THIEBAUD, R. S., ROSSOW, L. M., ABE, T., YE,
X., KIM, D. & BEMBEN, M. G. 2012c. The acute hemodynamic effects of
blood flow restriction in the absence of exercise. Clinical Physiology and
Functional Imaging.
LOENNEKE, J. P., FAHS, C. A., WILSON, J. M. & BEMBEN, M. G. 2011d. Blood
flow restriction: The metabolite/volume threshold theory. Medical Hypotheses,
In Press, Corrected Proof.
LOENNEKE, J. P., KEARNEY, M. L., THROWER, A. D., COLLINS, S. & PUJOL, T.
J. 2010b. The acute response of practical occlusion in the knee extensors. The
Journal of Strength & Conditioning Research, 24, 2831.
LOENNEKE, J. P., KIM, D., FAHS, C. A., THIEBAUD, R. S., ABE, T., LARSON, R.
D., BEMBEN, D. A. & BEMBEN, M. G. 2014d. Effects of exercise with and
without different degrees of blood flow restriction on torque and muscle
activation. Muscle & Nerve, 51(5), 713-721.
LOENNEKE, J. P., KIM, D., FAHS, C. A., THIEBAUD, R. S., ABE, T., LARSON, R.
D., BEMBEN, D. A. & BEMBEN, M. G. 2015. The effects of resistance
exercise with and without different degrees of blood-flow restriction on
perceptual responses. Journal of Sports Sciences, 1-8.
LOENNEKE, J. P., THIEBAUD, R., FAHS, C., ROSSOW, L., ABE, T. & BEMBEN,
M. 2014e. Blood flow restriction: effects of cuff type on fatigue and perceptual
responses to resistance exercise. Acta Physiologica Hungarica, 101, 158-166.
LOENNEKE, J. P., THIEBAUD, R. S., FAHS, C. A., ROSSOW, L. M., ABE, T. &
BEMBEN, M. G. 2012d. Blood flow restriction does not result in prolonged
decrements in torque. European Journal of Applied Physiology, 1-9.
LOENNEKE, J. P., THIEBAUD, R. S., FAHS, C. A., ROSSOW, L. M., ABE, T. &
BEMBEN, M. G. 2013b. Effect of cuff type on arterial occlusion. Clinical

295
LOENNEKE, J. P., THROWER, A. D., BALAPUR, A., BARNES, J. T. & PUJOL, T.
J. 2011e. The energy requirement of walking with restricted blood flow. Acta
Kinesiologica.
LOENNEKE, J. P., THROWER, A. D., BALAPUR, A., BARNES, J. T. & PUJOL, T.
J. 2012e. Blood flow–restricted walking does not result in an accumulation of
metabolites. Clinical Physiology and Functional Imaging.
LOENNEKE, J. P., WILSON, J. M., BALAPUR, A., THROWER, A. D., BARNES, J.
T. & PUJOL, T. J. 2012f. Time under tension decreased with blood flow–
restricted exercise. Clinical Physiology and Functional Imaging, 32, 268-273.
LOENNEKE, J. P., WILSON, J. M., MARIN, P. J., ZOURDOS, M. C. & BEMBEN,
M. G. 2011f. Low intensity blood flow restriction training: a meta-analysis.
LOENNEKE, J. P., YOUNG, K. C., WILSON, J. M. & ANDERSEN, J. 2012g.
Rehabilitation of an osteochondral fracture using blood flow restricted exercise:
A case review. Journal of Bodywork and Movement Therapies.
LOHMAN, M., TALLROTH, K., KETTUNEN, J. A. & MARTTINEN, M. T. 2009.
Reproducibility of dual-energy x-ray absorptiometry total and regional body
composition measurements using different scanning positions and definitions of
regions. Metabolism, 58, 1663-1668.
LOVELL, D. I., CUNEO, R. & GASS, G. C. 2009. Strength training improves
submaximum cardiovascular performance in older men. Journal of Geriatric
Physical Therapy, 32, 117.
LOVELL, D. I., CUNEO, R. & GASS, G. C. 2011. The blood pressure response of
older men to maximum and sub-maximum strength testing. Journal of Science
and Medicine in Sport.
LOWERY, R. P., JOY, J. M., LOENNEKE, J. P., DE SOUZA, E. O., MACHADO, M.,
DUDECK, J. E. & WILSON, J. M. 2013. Practical blood flow restriction
training increases muscle hypertrophy during a periodized resistance training
programme. Clinical Physiology and Functional Imaging, 34(4), 317-321.
LUEBBERS, P. E., FRY, A. C., KRILEY, L. M. & BUTLER, M. S. 2014. The Effects
of a Seven-week Practical Blood Flow Restriction Program on Well-trained
Collegiate Athletes. The Journal of Strength & Conditioning Research.
LUSIANI, L., RONSISVALLE, G., BONANOME, A., VISONA', A., CASTELLANI,
V., MACCHIA, C. & PAGNAN, A. 1986. Echocardiographic evaluation of the
dimensions and systolic properties of the left ventricle in freshman athletes
during physical training. European Heart Journal, 7, 196-203.
MACDOUGALL, J., TUXEN, D., SALE, D., MOROZ, J. & SUTTON, J. 1985.
Arterial blood pressure response to heavy resistance exercise. Journal of Applied
Physiology, 58, 785.
MADARAME, H., KURANO, M., TAKANO, H., IIDA, H., SATO, Y., OHSHIMA,
H., ABE, T., ISHII, N., MORITA, T. & NAKAJIMA, T. 2010a. Effects of low
intensity resistance exercise with blood flow restriction on coagulation system in
healthy subjects. Clinical Physiology and Functional Imaging, 30, 210-213.
MADARAME, H., NEYA, M., OCHI, E., NAKAZATO, K., SATO, Y. & ISHII, N.
2008. Cross-transfer effects of resistance training with blood flow restriction.
Medicine & Science in Sports & Exercise, 40, 258.
MADARAME, H., SASAKI, K. & ISHII, N. 2010b. Endocrine responses to upper-and
lower-limb resistance exercises with blood flow restriction. Acta Physiologica
Hungarica, 97, 192-200.
MANINI, T. & CLARK, B. 2009. Blood flow restricted exercise and skeletal muscle
health. Exercise and Sport Sciences Reviews, 37, 78.

296
MANINI, T. M., YARROW, J. F., BUFORD, T. W., CLARK, B. C., CONOVER, C. F.
& BORST, S. E. 2012. Growth hormone responses to acute resistance exercise
with vascular restriction in young and old men. Growth Hormone & IGF
Research.
MANN, T., LAMBERTS, R. & LAMBERT, M. 2014. High Responders and Low
Responders: Factors Associated with Individual Variation in Response to
Standardized Training. Sports Medicine, 1-12.
MARTÍN‐HERNÁNDEZ, J., MARÍN, P., MENÉNDEZ, H., FERRERO, C.,
LOENNEKE, J. & HERRERO, A. 2013. Muscular adaptations after two
different volumes of blood flow‐restricted training. Scandinavian Journal of
Medicine & Science in Sports.
MATTAR, M. A., GUALANO, B., PERANDINI, L. A., SHINJO, S. K., LIMA, F. R.,
SÁ-PINTO, A. L. & ROSCHEL, H. 2014. Safety and possible effects of low-
intensity resistance training associated with partial blood flow restriction in
polymyositis and dermatomyositis. Arthritis Research & Therapy, 16, 473.
MCCARTNEY, N., MCKELVIE, R., MARTIN, J., SALE, D. & MACDOUGALL, J.
1993. Weight-training-induced attenuation of the circulatory response of older
males to weight lifting. Journal of Applied Physiology, 74, 1056-1060.
MCEWEN, J. A., KELLY, D. L., JARDANOWSKI, T. & INKPEN, K. 2002.
Tourniquet safety in lower leg applications. Orthopaedic Nursing, 21, 61.
MCHUGH, M. P. 2003. Recent advances in the understanding of the repeated bout
effect: the protective effect against muscle damage from a single bout of
eccentric exercise. Scandinavian Journal of Medicine & Science in Sports, 13,
88-97.
MCKAY, W. B., STOKIC, D. S., SHERWOOD, A. M., VRBOVA, G. &
DIMITRIJEVIC, M. R. 1996. Effect of fatiguing maximal voluntary contraction
on excitatory and inhibitory responses elicited by transcranial magnetic motor
cortex stimulation. Muscle & Nerve, 19, 1017-1024.
MCKAY, W. B., TUEL, S. M., SHERWOOD, A. M., STOKIĆ, D. S. &
DIMITRIJEVIĆ, M. R. 1995. Focal depression of cortical excitability induced
by fatiguing muscle contraction: a transcranial magnetic stimulation study.
Experimental Brain Research, 105, 276-282.
MEDICINE, A. C. O. S. 2013. ACSM's guidelines for exercise testing and prescription,
Lippincott Williams & Wilkins.
MERLETTI, R. & PARKER, P. A. 2004. Electromyography: physiology, engineering,
and non-invasive applications, John Wiley & Sons.
MILES, D. S., OWENS, J. J., GOLDEN, J. C. & GOTSHALL, R. W. 1987. Central and
peripheral hemodynamics during maximal leg extension exercise. European
Journal of Applied Physiology and Occupational Physiology, 56, 12-17.
MILLET, G. Y., MARTIN, V., MARTIN, A. & VERGENS, S. 2011. Electrical
stimulation for testing neuromuscular function: from sport to pathology.
MILLET, G. Y., MUTHALIB, M., JUBEAU, M., LAURSEN, P. B. & NOSAKA, K.
2012. Severe hypoxia affects exercise performance independently of afferent
feedback and peripheral fatigue. Journal of Applied Physiology, 112, 1335-
1344.
MITTAL, P., SHENOY, S. & SANDHU, J. S. 2008. Effect of different cuff widths on
the motor nerve conduction of the median nerve: an experimental study. Journal
of Orthopaedic Surgery and Research, 3, 1.
MOON, J. R., ECKERSON, J. M., TOBKIN, S. E., SMITH, A. E., LOCKWOOD, C.
M., WALTER, A. A., CRAMER, J. T., BECK, T. W. & STOUT, J. R. 2009.
Estimating body fat in NCAA Division I female athletes: a five-compartment

297
model validation of laboratory methods. European Journal of Applied
MOORE, D., BURGOMASTER, K., SCHOFIELD, L., GIBALA, M., SALE, D. &
PHILLIPS, S. 2004. Neuromuscular adaptations in human muscle following low
intensity resistance training with vascular occlusion. European Journal of
MOORE, M., GARFIN, S. & HARGENS, A. 1987. Wide tourniquets eliminate blood
flow at low inflation pressures. The Journal of Hand Surgery, 12, 1006-1011.
MORAN, D., EPSTEIN, Y., KEREN, G., LAOR, A., SHEREZ, J. & SHAPIRO, Y.
1995. Calculation of mean arterial pressure during exercise as a function of heart
rate. Applied Human Sciences, 14, 293-5.
MORITA, T., FUKUDA, T., KIKUCHI, H., IKEDA, K., YUMOTO, M. & SATO, Y.
2010. Effects of blood flow restriction on cerebral blood flow during a single
arm-curl resistance exercise. International Journal of KAATSU Training
Research, 6, 9-12.
MORITANI, T. & DEVRIES, H. 1979. Neural factors versus hypertrophy in the time
course of muscle strength gain. American Journal of Physical Medicine, 58,
115.
MORITANI, T., SHERMAN, W. M., SHIBATA, M., MATSUMOTO, T. &
SHINOHARA, M. 1992. Oxygen availability and motor unit activity in humans.
European Journal of Applied Physiology and Occupupational Physiology, 64,
552-6.
MÜLLER, G. E. & PILZECKER, A. 1900. Experimentelle beiträge zur lehre vom
gedächtniss, JA Barth.
MUNN, J., HERBERT, R. & GANDEVIA, S. 2004. Contralateral effects of unilateral
resistance training: a meta-analysis. Journal of Applied Physiology, 96, 1861.
MUNN, J., HERBERT, R. D., HANCOCK, M. J. & GANDEVIA, S. C. 2005.
Resistance training for strength: effect of number of sets and contraction speed.
Medicine & Science in Sports & Exercise, 37, 1622.
NAKAJIMA, T., IIDA, H., KURANO, M., TAKANO, H., MORITA, T., MEGURO,
K., SATO, Y., YAMAZAKI, Y., KAWASHIMA, S. & OHSHIMA, H. 2008.
Hemodynamic responses to simulated weightlessness of 24-h head-down bed
rest and KAATSU blood flow restriction. European Journal of Applied
NAKAJIMA, T., KURANO, M., IIDA, H., TAKANO, H., OONUMA, H., MORITA,
T., MEGURO, K., SATO, Y. & NAGATA, T. 2006. Use and safety of
KAATSU training: results of a national survey. International Journal of
NAKAJIMA, T., KURANO, M., SAKAGAMI, F., IIDA, H., FUKUMURA, K.,
FUKUDA, T., TAKANO, H., MADARAME, H., YASUDA, T. & NAGATA,
T. 2010. Effects of low-intensity KAATSU resistance training on skeletal
muscle size/strength and endurance capacity in patients with ischemic heart
disease. International Journal of KAATSU Training Research, 6, 1-7.
NANA, A., SLATER, G. J., STEWART, A. D. & BURKE, L. M. 2015. Methodology
Review: Using Dual-Energy X-Ray Absorptiometry (DXA) for the Assessment
of Body Composition in Athletes and Active People. International Journal of
Sport Nutrition and Exercise Metabolism, 25, 198-215.
NARDONE, A., ROMANO, C. & SCHIEPPATI, M. 1989. Selective recruitment of
high-threshold human motor units during voluntary isotonic lengthening of
active muscles. The Journal of Physiology, 409, 451.
NARICI, M., HOPPELER, H., KAYSER, B., LANDONI, L., CLAASSEN, H.,
GAVARDI, C., CONTI, M. & CERRETELLI, P. 1996. Human quadriceps

298
cross sectional area, torque and neural activation during 6 months strength
training. Acta Physiologica Scandinavica, 157, 175-186.
NARICI, M., ROI, G., LANDONI, L., MINETTI, A. & CERRETELLI, P. 1989.
Changes in force, cross-sectional area and neural activation during strength
training and detraining of the human quadriceps. European Journal of Applied
Physiology and Occupational Physiology, 59, 310-319.
NELSON, R. R., GOBEL, F. L., JORGENSEN, C. R., WANG, K., WANG, Y. &
TAYLOR, H. L. 1974. Hemodynamic predictors of myocardial oxygen
consumption during static and dynamic exercise. Circulation, 50, 1179-1189.
NETO, G. R., SANTOS, H. H., SOUSA, J. B., JÚNIOR, A. T., ARAÚJO, J. P.,
ANICETO, R. R. & SOUSA, M. S. 2014a. Effects of High-Intensity Blood
Flow Restriction Exercise on Muscle Fatigue. Journal of Human Kinetics, 41,
163-172.
NETO, G. R., SOUSA, M. S. C., COSTA E SILVA, G. V., GIL, A. L. S., SALLES, B.
F. & NOVAES, J. S. 2014b. Acute resistance exercise with blood flow
restriction effects on heart rate, double product, oxygen saturation and perceived
exertion. Clinical Physiology and Functional Imaging.
NIELSEN, J. L., AAGAARD, P., BECH, R. D., NYGAARD, T., HVID, L. G.,
WERNBOM, M., SUETTA, C. & FRANDSEN, U. 2012. Proliferation of
myogenic stem cells in human skeletal muscle in response to low‐load resistance
training with blood flow restriction. The Journal of Physiology.
NOLTE, J. 2002. The Human Brain: An Introduction to Its Functional Anatomy,
Philadelphia, USA, Mosby.
NOSAKA, K. & CLARKSON, P. M. 1995. Muscle damage following repeated bouts of
high force eccentric exercise. Medicine and Science in Sports and Exercise, 27,
1263-1269.
NOSAKA, K., SAKAMOTO, K., NEWTON, M. & SACCO, P. 2001. How long does
the protective effect on eccentric exercise-induced muscle damage last?
Medicine and Science in Sports and Exercise, 33, 1490-1495.
NUZZO, J. L., BARRY, B. K., GANDEVIA, S. C. & TAYLOR, J. L. 2015. Acute
Strength Training Increases Responses to Stimulation of Corticospinal Axons.
Medicine and Science in Sports and Exercise.
NYGREN, A., SUNDBERG, C., ESBJVARNSSON-LILJEDAHL, M., JANSSON, E.
& KAIJSER, L. 2000. Effects of dynamic ischaemic training on human skeletal
muscle dimensions. European Journal of Applied Physiology, 82, 137-141.
OGAWA, M., LOENNEKE, J. P., YASUDA, T., FAHS, C. A., ROSSOW, L. M.,
THIEBAUD, R. S., BEMBEN, M. G. & ABE, T. 2012. Time course changes in
muscle size and fatigue during walking with restricted leg blood flow in young
men. Journal of Physical Education and Sports Management, 3, 14-19.
OHTA, H., KUROSAWA, H., IKEDA, H., IWASE, Y., SATOU, N. & NAKAMURA,
S. 2003. Low-load resistance muscular training with moderate restriction of
blood flow after anterior cruciate ligament reconstruction. Acta Orthopaedica,
74, 62-68.
OKITA, K. & TAKADA, S. 2013. Application of Blood Flow Restriction in Resistance
Exercise Assessed by Intramuscular Metabolic Stress. Journal of Novel
Physiotherapies, 3, 2.
OKUNO, N. M., PEDRO, R. E., LEICHT, A. S., DE PAULA RAMOS, S. &
NAKAMURA, F. Y. 2014. Cardiac Autonomic Recovery After a Single Session
of Resistance Exercise With and Without Vascular Occlusion. The Journal of
Strength & Conditioning Research, 28, 1143-1150.
OZAKI, H., BRECHUE, W. F., SAKAMAKI, M., YASUDA, T., NISHIKAWA, M.,
AOKI, N., OGITA, F. & ABE, T. 2010. Metabolic and cardiovascular responses

299
to upright cycle exercise with leg blood flow reduction. Journal of Sports
Science and Medicine, 9, 224-230.
OZAKI, H., MIYACHI, M., NAKAJIMA, T. & ABE, T. 2011a. Effects of 10 Weeks
Walk Training With Leg Blood Flow Reduction on Carotid Arterial Compliance
and Muscle Size in the Elderly Adults. Angiology, 62, 81.
OZAKI, H., SAKAMAKI, M., YASUDA, T., FUJITA, S., OGASAWARA, R.,
SUGAYA, M., NAKAJIMA, T. & ABE, T. 2011b. Increases in Thigh Muscle
Volume and Strength by Walk Training with Leg Blood Flow Reduction in
Older Participants. The Journals of Gerontology Series A: Biological Sciences
and Medical Sciences, 66, 257.
OZAKI, H., YASUDA, T., OGASAWARA, R., SAKAMAKI-SUNAGA, M., NAITO,
H. & ABE, T. 2012. Effects of high-intensity and blood flow-restricted low-
intensity resistance training on carotid arterial compliance: role of blood
pressure during training sessions. European Journal of Applied Physiology, 1-8.
PARK, S., KIM, J. K., CHOI, H. M., KIM, H. G., BEEKLEY, M. D. & NHO, H. 2010.
Increase in maximal oxygen uptake following 2-week walk training with blood
flow occlusion in athletes. European Journal of Applied Physiology, 109, 591-
600.
PASCUAL-LEONE, A., GRAFMAN, J. & HALLETT, M. 1994. Modulation of
cortical motor output maps during development of implicit and explicit
knowledge. Science, 263, 1287-1289.
PASCUAL-LEONE, A., NGUYET, D., COHEN, L. G., BRASIL-NETO, J. P.,
CAMMAROTA, A. & HALLETT, M. 1995. Modulation of muscle responses
evoked by transcranial magnetic stimulation during the acquisition of new fine
motor skills. Journal of Neurophysiology, 74, 1037-45.
PATTEN, C., KAMEN, G. & ROWLAND, D. 2001. Adaptations in maximal motor
unit discharge rate to strength training in young and older adults. Muscle &
Nerve, 24, 542-550.
PATTERSON, S. D. & FERGUSON, R. A. 2010. Increase in calf post-occlusive blood
flow and strength following short-term resistance exercise training with blood
flow restriction in young women. European Journal of Applied Physiology, 108,
1025-1033.
PEARCE, A., HENDY, A., BOWEN, W. & KIDGELL, D. 2012. Corticospinal
adaptations and strength maintenance in the immobilized arm following 3 weeks
unilateral strength training. Scandinavian Journal of Medicine & Science in
Sports.
PEARCE, A. J. & KIDGELL, D. J. 2009. Neuroplasticity Following Skill and Strength
Training: Evidence from Transcranial Magnetic Stimulation Studies.
PEARSON, A. C., SCHIFF, M., MROSEK, D., LABOVITZ, A. J. & WILLIAMS, G.
A. 1986. Left ventricular diastolic function in weight lifters. The American
journal of cardiology, 58, 1254-1259.
PEARSON, S. J. & HUSSAIN, S. R. 2014. A Review on the Mechanisms of Blood-
Flow Restriction Resistance Training-Induced Muscle Hypertrophy. Sports
Medicine, 1-14.
PEREZ, M. A. & COHEN, L. G. 2008. Mechanisms underlying functional changes in
the primary motor cortex ipsilateral to an active hand. The Journal of
Neuroscience, 28, 5631-5640.
PEREZ, M. A., LUNGHOLT, B. K. S., NYBORG, K. & NIELSEN, J. B. 2004. Motor
skill training induces changes in the excitability of the leg cortical area in
healthy humans. Experimental Brain Research, 159, 197-205.

300
PESCATELLO, L. S., FARGO, A. E., LEACH, C. & SCHERZER, H. H. 1991. Short-
term effect of dynamic exercise on arterial blood pressure. Circulation, 83,
1557-1561.
PESCATELLO, L. S., FRANKLIN, B. A., FAGARD, R., FARQUHAR, W. B.,
KELLEY, G. A. & RAY, C. A. 2004. Exercise and hypertension. Medicine &
Science in Sports & Exercise, 36, 533.
PICKERING, T. G., HALL, J. E., APPEL, L. J., FALKNER, B. E., GRAVES, J.,
HILL, M. N., JONES, D. W., KURTZ, T., SHEPS, S. G. & ROCCELLA, E. J.
2005. Recommendations for blood pressure measurement in humans and
experimental animals: Part 1: Blood pressure measurement in humans: a
statement for professionals from the Subcommittee of Professional and Public
Education of the American Heart Association Council on High Blood Pressure
Research. Hypertension, 45, 142-161.
PIEPOLI, M. F., CONRAADS, V., CORRA, U., DICKSTEIN, K., FRANCIS, D. P.,
JAARSMA, T., MCMURRAY, J., PIESKE, B., PIOTROWICZ, E. &
SCHMID, J. P. 2011. Exercise training in heart failure: from theory to practice.
A consensus document of the Heart Failure Association and the European
Association for Cardiovascular Prevention and Rehabilitation. European
Journal of Heart Failure, 13, 347-357.
PIERCE, J., CLARK, B., PLOUTZ-SNYDER, L. & KANALEY, J. 2006. Growth
hormone and muscle function responses to skeletal muscle ischemia. Journal of
Applied Physiology, 101, 1588.
PLUIM, B. M., ZWINDERMAN, A. H., VAN DER LAARSE, A. & VAN DER
WALL, E. E. 2000. The athlete’s heart a meta-analysis of cardiac structure and
function. Circulation, 101, 336-344.
POLLOCK, M. L., GRAVES, J. E., SWART, D. L. & LOWENTHAL, D. T. 1994.
Exercise training and prescription for the elderly. Southern Medical Journal, 87,
S88.
POPE, Z. K., WILLARDSON, J. M. & SCHOENFELD, B. J. 2013. A Brief Review:
Exercise and Blood Flow Restriction. The Journal of Strength & Conditioning
Research, Publish Ahead of Print, 10.1519/JSC.0b013e3182874721.
PORTER, R. 1985. The corticomotoneuronal component of the pyramidal tract:
corticomotoneuronal connections and functions in primates. Brain Research,
357, 1-26.
PORTER, R. & LEMON, R. N. 1993. Corticospinal Function and Voluntary
Movement, New York, USA, Oxford Science Publications.
POTON, R. & POLITO, M. D. 2014. Hemodynamic response to resistance exercise
with and without blood flow restriction in healthy subjects. Clinical Physiology
and Functional Imaging.
PRIOR, B. M., LLOYD, P. G., YANG, H. & TERJUNG, R. L. 2003. Exercise-induced
vascular remodeling. Exercise and Sport Sciences Reviews, 31, 26-33.
RANTALAINEN, T., WEIER, A., LEUNG, M., BRANDNER, C., SPITTLE, M. &
KIDGELL, D. 2013. Short-interval intracortical inhibition is not affected by
varying visual feedback in an isometric task in biceps brachii muscle. Frontiers
in Human Neuroscience, 7.
REEVES, G. V., KRAEMER, R. R., HOLLANDER, D. B., CLAVIER, J., THOMAS,
C., FRANCOIS, M. & CASTRACANE, V. D. 2006. Comparison of hormone
responses following light resistance exercise with partial vascular occlusion and
moderately difficult resistance exercise without occlusion. Journal of Applied

301
REEVES, N. D., MAGANARIS, C. N. & NARICI, M. V. 2004. Ultrasonographic
assessment of human skeletal muscle size. European Journal of Applied
REIS, J., SWAYNE, O. B., VANDERMEEREN, Y., CAMUS, M., DIMYAN, M. A.,
HARRIS-LOVE, M., PEREZ, M. A., RAGERT, P., ROTHWELL, J. C. &
COHEN, L. G. 2008. Contribution of transcranial magnetic stimulation to the
understanding of cortical mechanisms involved in motor control. The Journal Of
RENNIE, M. 2003. Claims for the anabolic effects of growth hormone: a case of the
emperor’s new clothes? British journal of sports medicine, 37, 100-105.
RENZI, C. P., TANAKA, H. & SUGAWARA, J. 2010. Effects of leg blood flow
restriction during walking on cardiovascular function. Medicine & Science in
Sports & Exercise, 42, 726.
RHEA, M. R. 2004. Determining the magnitude of treatment effects in strength training
research through the use of the effect size. The Journal of Strength &
RIDDING, M. & ROTHWELL, J. 1995. Reorganisation in human motor cortex.
Canadian Journal of Physiology and Pharmacology, 73, 218-222.
RIDDING, M. C. & ROTHWELL, J. C. 1997. Stimulus/response curves as a method of
measuring motor cortical excitability in man. Electroencephalogr Clin
Neurophysiol, 105, 340-4.
ROONEY, K., HERBERT, R. & BALNAVE, R. 1994. Fatigue contributes to the
strength training stimulus. Medicine & Science in Sports & Exercise, 26, 1160.
ROSENKRANZ, K. & ROTHWELL, J. C. 2006. Differences between the effects of
three plasticity inducing protocols on the organization of the human motor
cortex. European Journal of Neuroscience, 23, 822-829.
ROSSI, S., HALLETT, M., ROSSINI, P. M. & PASCUAL-LEONE, A. 2009. Safety,
ethical considerations, and application guidelines for the use of transcranial
magnetic stimulation in clinical practice and research. Clinical
ROSSINI, P. M., BARKER, A. T., BERARDELLI, A., CARAMIA, M., CARUSO, G.,
CRACCO, R. Q., DIMITRIJEVIC, M. R., HALLETT, M., KATAYAMA, Y.,
LUCKING, C. H., MAERTENS DE NOORDHOUT, A., MARSDEN, C. D.,
MURRAY, N. M. F., ROTHWELL, J. C., SWOSH, M. & TOMBERG, C. 1994.
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and
roots: basic principles and procedures for routine clinical application. Report of
an IFCN committee. Electroencephalography and Clinical Neurophysiology 91,
79-92.
ROSSOW, L. M., FAHS, C. A., LOENNEKE, J. P., THIEBAUD, R. S., SHERK, V.
D., ABE, T. & BEMBEN, M. G. 2012. Cardiovascular and perceptual responses
to blood flow restricted resistance exercise with differing restrictive cuffs.
Clinical Physiology and Functional Imaging.
ROSSOW, L. M., FAHS, C. A., SHERK, V. D., SEO, D., BEMBEN, D. A. &
BEMBEN, M. G. 2011. The effect of acute blood-flow-restricted resistance
exercise on postexercise blood pressure. Clinical Physiology and Functional
Imaging.
ROTH, S. M., MARTEL, G. F., FERRELL, R. E., METTER, E. J., HURLEY, B. F. &
ROGERS, M. A. 2003. Myostatin gene expression is reduced in humans with
heavy-resistance strength training: a brief communication. Experimental Biology
and Medicine, 228, 706-709.
ROTHWELL, J. C. 1994. Control of Voluntary Human Movement, London, Chapman
& Hall.

302
ROTTO, D. M. & KAUFMAN, M. P. 1988. Effect of metabolic products of muscular
contraction on discharge of group III and IV afferents. Journal of Applied
Physiology, 64, 2306-2313.
RUPP, T., JUBEAU, M., WUYAM, B., PERREY, S., LEVY, P., MILLET, G. Y. &
VERGES, S. 2012. Time-dependent effect of acute hypoxia on corticospinal
excitability in healthy humans. Journal of Neurophysiology, 108, 1270-1277.
SACCO, P., THICKBROOM, G. W., BYRNES, M. L. & MASTAGLIA, F. L. 2000.
Changes in corticomotor excitability after fatiguing muscle contractions. Muscle
& Nerve, 23, 1840-1846.
SACCO, P., THICKBROOM, G. W., THOMPSON, M. L. & MASTAGLIA, F. L.
1997. Changes in corticomotor excitation and inhibition during prolonged
submaximal muscle contractions. Muscle & Nerve, 20, 1158-1166.
SAKAMAKI-SUNAGA, M., LOENNEKE, J., THIEBAUD, R. & ABE, T. 2012. Onset
of blood lactate accumulation and peak oxygen uptake during graded walking
test combined with and without restricted leg blood flow. Comparative Exercise
Physiology, 1-6.
SAKAMAKI, M., FUJITA, S., SATO, Y., BEMBEN, M. & ABE, T. 2008. Blood
pressure response to slow walking combined with KAATSU in the elderly.
SAKURABA, K. & ISHIKAWA, T. 2009. Effect of isokinetic resistance training under
a condition of restricted blood flow with pressure. Journal of Orthopaedic
Science, 14, 631-639.
SALE, D. 1987. Influence of Exercise and Training on Motor Unit Activation. Exercise
and Sport Sciences Reviews, 15, 95.
SALE, D. 1988. Neural adaptation to resistance training. Medicine & Science in Sports
& Exercise, 20, S135.
SALE, D., MOROZ, D., MCKELVIE, R., MACDOUGALL, J. & MCCARTNEY, N.
1993. Comparison of blood pressure response to isokinetic and weight-lifting
exercise. European Journal of Applied Physiology and Occupational
SALE, D. G., MOROZ, D. E., MCKELVIE, R. S., MACDOUGALL, J. D. &
MCCARTNEY, N. 1994. Effect of training on the blood pressure response to
weight lifting. Canadian Journal of Applied Physiology, 19, 60-74.
SAMII, A., WASSERMANN, E., IKOMA, K., MERCURI, B. & HALLETT, M. 1996.
Characterization of postexercise facilitation and depression of motor evoked
potentials to transcranial magnetic stimulation. Neurology, 46, 1376-1376.
SANES, J. N. & DONOGHUE, J. P. 2000. Plasticity and primary motor cortex. Annual
Review of Neuroscience, 23, 393-415.
SATO, Y. 2005. The history and future of KAATSU training. International Journal of
SATOH, I. 2011. Kaatsu training: application to metabolic syndrome. International
SCHMIDT, M. W., HINDER, M. R., SUMMERS, J. J. & GARRY, M. I. 2011. Long-
lasting contralateral motor cortex excitability is increased by unilateral hand
movement that triggers electrical stimulation of opposite homologous muscles.
Neurorehabilitation and Neural repair, 25, 521-530.
SCHOENFELD, B. 2013. Is There a Minimum Intensity Threshold for Resistance
Training-Induced Hypertrophic Adaptations? Sports Medicine, 1-10.
SCHOENFELD, B. J. 2012. Does exercise-induced muscle damage play a role in
skeletal muscle hypertrophy? The Journal of Strength & Conditioning Research,
26, 1441-1453.

303
SCHOENFELD, B. J., PETERSON, M. D., OGBORN, D., CONTRERAS, B. &
SONMEZ, G. T. 2015. Effects of Low- Versus High-Load Resistance Training
on Muscle Strength and Hypertrophy in Well-Trained Men. The Journal of
Strength & Conditioning Research, Publish Ahead of Print.
SCHUBERT, M., BECK, S., TAUBE, W., AMTAGE, F., FAIST, M. & GRUBER, M.
2008. Balance training and ballistic strength training are associated with task‐
specific corticospinal adaptations. European Journal of Neuroscience, 27, 2007-
2018.
SCOTT, B. R., LOENNEKE, J. P., SLATTERY, K. M. & DASCOMBE, B. J. 2014.
Exercise with Blood Flow Restriction: An Updated Evidence-Based Approach
for Enhanced Muscular Development. Sports Medicine.
SEIDLER, R. D. 2010. Neural correlates of motor learning, transfer of learning, and
learning to learn. Exercise and Sport Sciences Reviews, 38, 3.
SELVANAYAGAM, V. S., RIEK, S. & CARROLL, T. J. 2011. Early neural responses
to strength training. Journal of Applied Physiology.
SEO, D.-I., KIM, E., FAHS, C. A., ROSSOW, L., YOUNG, K., FERGUSON, S. L.,
THIEBAUD, R., SHERK, V. D., LOENNEKE, J. P., KIM, D., LEE, M.-K.,
CHOI, K.-H., BEMBEN, D. A., BEMBEN, M. G. & SO, W.-Y. 2012.
Reliability of the One-Repetition Maximum Test Based on Muscle Group and
Gender. Journal of Sports Science & Medicine, 11, 221-225.
SHABKHIZ, F., GHARAHDAGHI, N., ALVAR, Y. & AMIRSHAGHAGHI, F. 2013.
Adaptations of cardiac morphology and function to Duration of Resistance
Training in Untrained Females. 85, 1-7.
SHADMEHR, R. & HOLCOMB, H. H. 1997. Neural correlates of motor memory
consolidation. Science, 277, 821-825.
SHAW, J. A. & MURRAY, D. G. 1982. The relationship between tourniquet pressure
and underlying soft-tissue pressure in the thigh. Journal of Bone Joint Surgery
of America, 64, 1148-52.
SHINOHARA, M., KOUZAKI, M., YOSHIHISA, T. & FUKUNAGA, T. 1998.
Efficacy of tourniquet ischemia for strength training with low resistance.
European Journal of Applied Physiology and Occupational Physiology, 77, 189-
191.
SILVA, A., MINDERICO, C., TEIXEIRA, P., PIETROBELLI, A. & SARDINHA, L.
2006. Body fat measurement in adolescent athletes: multicompartment
molecular model comparison. European Journal of Clinical Nutrition, 60, 955-
964.
SMITH, M. L. & RAVEN, P. B. 1986. Cardiovascular responses to lower body
negative pressure in endurance and static exercise-trained men. Medicine and
Science in Sports and Exercise, 18, 545-550.
SØGAARD, K., GANDEVIA, S. C., TODD, G., PETERSEN, N. T. & TAYLOR, J. L.
2006. The effect of sustained low-intensity contractions on supraspinal fatigue
in human elbow flexor muscles. The Journal of Physiology, 573, 511-523.
SOMMER, M., TERGAU, F., WISCHER, S. & PAULUS, W. 2001. Paired-pulse
repetitive transcranial magnetic stimulation of the human motor cortex.
Experimental Brain Research, 139, 465-472.
STARON, R. S., LEONARDI, M. J., KARAPONDO, D. L., MALICKY, E. S.,
FALKEL, J. E., HAGERMAN, F. C. & HIKIDA, R. S. 1991. Strength and
skeletal muscle adaptations in heavy-resistance-trained women after detraining
and retraining. Journal of Applied Physiology, 70, 631-40.
STONE, W. J. & COULTER, S. P. 1994. Strength/endurance effects from three
resistance training protocols with women. Journal of Strength and Conditioning
Research, 8, 231-234.

304
SUGA, T., OKITA, K., MORITA, N., YOKOTA, T., HIRABAYASHI, K.,
HORIUCHI, M., TAKADA, S., TAKAHASHI, T., OMOKAWA, M. &
KINUGAWA, S. 2009. Intramuscular metabolism during low-intensity
resistance exercise with blood flow restriction. Journal of Applied Physiology,
106, 1119.
SUGA, T., OKITA, K., TAKADA, S., OMOKAWA, M., KADOGUCHI, T.,
YOKOTA, T., HIRABAYASHI, K., TAKAHASHI, M., MORITA, N. &
HORIUCHI, M. 2012. Effect of multiple set on intramuscular metabolic stress
during low-intensity resistance exercise with blood flow restriction. European
SUMIDE, T., SAKURABA, K., SAWAKI, K., OHMURA, H. & TAMURA, Y. 2009.
Effect of resistance exercise training combined with relatively low vascular
occlusion. Journal of Science and Medicine in Sport, 12, 107-112.
SUNDBERG, C. 1994. Exercise and training during graded leg ischaemia in healthy
man with special reference to effects on skeletal muscle. Acta physiologica
Scandinavica. Supplementum, 615, 1.
TAKADA, S., OKITA, K., SUGA, T., OMOKAWA, M., KADOGUCHI, T., SATO,
T., TAKAHASHI, M., YOKOTA, T., HIRABAYASHI, K. & MORITA, N.
2012. Low-intensity exercise can increase muscle mass and strength
proportionally to enhanced metabolic stress under ischemic conditions. Journal
of Applied Physiology, 113, 199-205.
TAKANO, H., MORITA, T., IIDA, H., ASADA, K., KATO, M., UNO, K., HIROSE,
K., MATSUMOTO, A., TAKENAKA, K. & HIRATA, Y. 2005. Hemodynamic
and hormonal responses to a short-term low-intensity resistance exercise with
the reduction of muscle blood flow. European Journal of Applied Physiology,
95, 65-73.
TAKARADA, Y., NAKAMURA, Y., ARUGA, S., ONDA, T., MIYAZAKI, S. &
ISHII, N. 2000a. Rapid increase in plasma growth hormone after low-intensity
resistance exercise with vascular occlusion. Journal of Applied Physiology, 88,
61.
TAKARADA, Y., SATO, Y. & ISHII, N. 2002. Effects of resistance exercise combined
with vascular occlusion on muscle function in athletes. European Journal of
TAKARADA, Y., TAKAZAWA, H. & ISHII, N. 2000b. Applications of vascular
occlusion diminish disuse atrophy of knee extensor muscles. Medicine &
Science in Sports & Exercise, 32, 2035.
TAKARADA, Y., TAKAZAWA, H., SATO, Y., TAKEBAYASHI, S., TANAKA, Y.
& ISHII, N. 2000c. Effects of resistance exercise combined with moderate
vascular occlusion on muscular function in humans. Journal of Applied
TAKARADA, Y., TSURUTA, T. & ISHII, N. 2004. Cooperative effects of exercise
and occlusive stimuli on muscular function in low-intensity resistance exercise
with moderate vascular occlusion. The Japanese Journal of Physiology, 54, 585-
592.
TAN, B. 1999. Manipulating resistance training program variables to optimize
maximum strength in men: a review. Journal of Strength and Conditioning
Research, 13, 289-304.
TANIMOTO, M., SANADA, K., YAMAMOTO, K., KAWANO, H., GANDO, Y.,
TABATA, I., ISHII, N. & MIYACHI, M. 2008. Effects of whole-body low-
intensity resistance training with slow movement and tonic force generation on
muscular size and strength in young men. The Journal of Strength &

305
TEO, W., RODRIGUES, J., MASTAGLIA, F. & THICKBROOM, G. 2012. Post-
exercise depression in corticomotor excitability after dynamic movement: a
general property of fatiguing and non-fatiguing exercise. Experimental Brain
Research, 216, 41-49.
TERAMOTO, M. & GOLDING, L. A. 2006. Low-intensity exercise, vascular
occlusion, and muscular adaptations. Research in sports medicine (Print), 14,
259.
TERAO, Y. & UGAWA, Y. 2002. Basic Mechanisms of TMS. Journal of Clinical
THIEBAUD, R. S. 2012. Exercise-Induced Muscle Damage: Is it detrimental or
beneficial? Journal of Trainology, 1, 36-44.
THIEBAUD, R. S., LOENNEKE, J. P., FAHS, C. A., ROSSOW, L. M., KIM, D.,
ABE, T., ANDERSON, M. A., YOUNG, K. C., BEMBEN, D. A. & BEMBEN,
M. G. 2013a. The effects of elastic band resistance training combined with
blood flow restriction on strength, total bone‐free lean body mass and muscle
thickness in postmenopausal women. Clinical Physiology and Functional
Imaging.
THIEBAUD, R. S., YASUDA, T., LOENNEKE, J. P. & ABE, T. 2013b. Effects of
low-intensity concentric and eccentric exercise combined with blood flow
restriction on indices of exercise-induced muscle damage. Interventional
Medicine and Applied Science, 5, 53-59.
THOIRS, K. & ENGLISH, C. 2009. Ultrasound measures of muscle thickness: intra‐
examiner reliability and influence of body position. Clinical Physiology and
Functional Imaging, 29, 440-446.
THOMPSON, H., CLARKSON, P. & SCORDILIS, S. 2002. The repeated bout effect
and heat shock proteins: intramuscular HSP27 and HSP70 expression following
two bouts of eccentric exercise in humans. Acta Physiologica Scandinavica,
174, 47-56.
TOIGO, M., ITEM, F., DENKINGER, J., FONTANA, P., WEBER, M. &
BOUTELLIER, U. 2010. Effects Of Vibration Exercise With Superimposed
Resistance Exercise And Vascular Occlusion On Muscle In Women. Medicine
& Science in Sports & Exercise, 42, 27.
TRAN, Q. T., DOCHERTY, D. & BEHM, D. 2006. The effects of varying time under
tension and volume load on acute neuromuscular responses. European Journal
of Applied Physiology, 98, 402-410.
TSUTSUMI, T., DON, B. M., ZAICHKOWSKY, L. D. & DELIZONNA, L. L. 1997.
Physical fitness and psychological benefits of strength training in community
dwelling older adults. Applied Human Science, 16, 257-266.
UMBEL, J. D., HOFFMAN, R. L., DEARTH, D. J., CHLEBOUN, G. S., MANINI, T.
M. & CLARK, B. C. 2009. Delayed-onset muscle soreness induced by low-load
blood flow-restricted exercise. European Journal of Applied Physiology, 107,
687-695.
VALLENCE, A.-M., HAMMOND, G. R. & REILLY, K. T. 2012. Increase in flexor
but not extensor corticospinal motor outputs following ischemic nerve block.
Journal of Neurophysiology, 107, 3417-3427.
VAN ROEKEL, H. & THURSTON, A. 1985. Tourniquet pressure: the effect of limb
circumference and systolic blood pressure. The Journal of Hand Surgery:
British & European Volume, 10, 142-144.
VANHEES, L., GELADAS, N., HANSEN, D., KOUIDI, E., NIEBAUER, J., REINER,
Ž., CORNELISSEN, V., ADAMOPOULOS, S., PRESCOTT, E. &
BÖRJESSON, M. 2012. Importance of characteristics and modalities of
physical activity and exercise in the management of cardiovascular health in

306
individuals with cardiovascular risk factors: recommendations from the EACPR
(Part II). European journal of preventive cardiology, 19, 1005-1033.
VIEIRA, A., GADELHA, A. B., FERREIRA-JUNIOR, J. B., VIEIRA, C. A., DE
MELO KEENE VON KOENIG SOARES, E., CADORE, E. L., WAGNER, D.
R. & BOTTARO, M. 2014. Session rating of perceived exertion following
resistance exercise with blood flow restriction. Clinical Physiology and
Functional Imaging.
VIEIRA, P. J. C., CHIAPPA, G. R., UMPIERRE, D., STEIN, R. & RIBEIRO, J. P.
2012. Hemodynamic Responses to Resistance Exercise With Restricted Blood
Flow in Young and Older Men. The Journal of Strength & Conditioning
Research.
VIERCK, J., O'REILLY, B., HOSSNER, K., ANTONIO, J., BYRNE, K., BUCCI, L. &
DODSON, M. 2000. Satellite cell regulation following myotrauma caused by
resistance exercise. Cell Biology International, 24, 263-272.
WASSERMANN, E., EPSTEIN, C. M. & ZIEMANN, U. 2008. The Oxford handbook
of transcranial stimulation, Oxford University Press, USA.
WEATHERHOLT, A., BEEKLEY, M., GREER, S., URTEL, M. & MIKESKY, A.
2012. Modified KAATSU Training: Adaptations and Subject Perceptions.
Medicine and Science in Sports and Exercise.
WEBER, M. & EISEN, A. A. 2002. Magnetic stimulation of the central and peripheral
nervous systems. Muscle and Nerve, 25, 160-75.
WEIER, A. T. & KIDGELL, D. J. 2012. Strength Training with Superimposed Whole
Body Vibration Does Not Preferentially Modulate Cortical Plasticity. The
Scientific World Journal, 2012.
WEIER, A. T., PEARCE, A. J. & KIDGELL, D. J. 2012. Strength training reduces
intracortical inhibition. Acta Physiologica, 206, 109-119.
WEISS, T., MILTNER, W. H. R., LIEPERT, J., MEISSNER, W. & TAUB, E. 2004.
Rapid functional plasticity in the primary somatomotor cortex and perceptual
changes after nerve block. European Journal of Neuroscience, 20, 3413-3423.
WERNBOM, M., AUGUSTSSON, J. & RAASTAD, T. 2006. Effects of vascular
occlusion on muscular endurance in dynamic knee extension exercise at
different submaximal loads. The Journal of Strength & Conditioning Research,
20, 372.
WERNBOM, M., AUGUSTSSON, J. & RAASTAD, T. 2008. Ischemic strength
training: a low load alternative to heavy resistance exercise? Scandinavian
Journal of Medicine & Science in Sports, 18, 401-416.
WERNBOM, M., JÄRREBRING, R., ANDREASSON, M. A. & AUGUSTSSON, J.
2009. Acute effects of blood flow restriction on muscle activity and endurance
during fatiguing dynamic knee extensions at low load. The Journal of Strength
& Conditioning Research, 23, 2389.
WERNBOM, M., PAULSEN, G., NILSEN, T. S., HISDAL, J. & RAASTAD, T.
2012a. Contractile function and sarcolemmal permeability after acute low-load
resistance exercise with blood flow restriction. European Journal of Applied
Physiology, 112, 2051-2063.
WERNBOM, M., PAULSEN, G., NILSEN, T. S., HISDAL, J. & RAASTAD, T.
2012b. Sarcolemmal permeability and muscle damage as hypertrophic stimuli in
blood flow restricted resistance exercise (Reply to Loenneke and Abe).
WERNBOM, M., APRO, W., PAULSEN, G., NILSEN, T., BLOMSTRAND, E.,
RAASTAD, T. 2013. Acute low-load resistance exercise with and without blood
flow restriction increased protein signalling and number of satellite cells in
human skeletal muscle. European Journal of Applied Physiology, 1-13.

307
WEST, D. & PHILLIPS, S. M. 2010. Anabolic processes in human skeletal muscle:
restoring the identities of growth hormone and testosterone. The Physician and
Sports Medicine, 38, 97-104.
WILLIAMS, M. A., HASKELL, W. L., ADES, P. A., AMSTERDAM, E. A.,
BITTNER, V., FRANKLIN, B. A., GULANICK, M., LAING, S. T. &
STEWART, K. J. 2007. Resistance exercise in individuals with and without
cardiovascular disease: 2007 update a scientific statement from the American
heart association council on clinical cardiology and council on nutrition,
physical activity, and metabolism. Circulation, 116, 572-584.
WILSON, J. M., LOWERY, R. P., JOY, J. M., LOENNEKE, J. P. & NAIMO, M. A.
2013. Practical blood flow restriction training increases acute determinants of
hypertrophy without increasing indices of muscle damage. The Journal of
WILSON, S., LOCKWOOD, R., THICKBROOM, G. & MASTAGLIA, F. 1993. The
muscle silent period following transcranial magnetic cortical stimulation.
Journal of the Neurological Sciences, 114, 216-222.
YAMANAKA, T., FARLEY, R. S. & CAPUTO, J. L. 2012. Occlusion training
increases muscular strength in division Ia football players. The Journal of
YASUDA, T., ABE, T., BRECHUE, W. F., IIDA, H., TAKANO, H., MEGURO, K.,
KURANO, M., FUJITA, S. & NAKAJIMA, T. 2010a. Venous blood gas and
metabolite response to low-intensity muscle contractions with external limb
compression. Metabolism, 59, 1510-1519.
YASUDA, T., ABE, T., SATO, Y., MIDORIKAWA, T., KEARNS, C., INOUE, K.,
RYUSHI, T. & ISHII, N. 2005. Muscle fiber cross-sectional area is increased
after two weeks of twice daily KAATSU-resistance training. International
YASUDA, T., BRECHUE, W. F., FUJITA, T., SATO, Y. & ABE, T. 2008. Muscle
activation during low-intensity muscle contractions with varying levels of
external limb compression. Journal of Sports Science and Medicine, 7, 467-474.
YASUDA, T., BRECHUE, W. F., FUJITA, T., SHIRAKAWA, J., SATO, Y. & ABE,
T. 2009. Muscle activation during low-intensity muscle contractions with
restricted blood flow. Journal of Sports Sciences, 27, 479-489.
YASUDA, T., FUJITA, S., OGASAWARA, R., SATO, Y. & ABE, T. 2010b. Effects
of low intensity bench press training with restricted arm muscle blood flow on
chest muscle hypertrophy: a pilot study. Clinical Physiology and Functional
Imaging, 30, 338-343.
YASUDA, T., FUJITA, T., MIYAGI, Y., KUBOTA, Y., SATO, Y., NAKAJIMA, T.,
BEMBEN, M. & ABE, T. 2006. Electromyographic responses of arm and chest
muscle during bench press exercise with and without KAATSU. International
YASUDA, T., FUKUMURA, K., FUKUDA, T., IIDA, H., IMUTA, H., SATO, Y.,
YAMASOBA, T. & NAKAJIMA, T. 2012a. Effects of low-intensity, elastic
band resistance exercise combined with blood flow restriction on muscle
activation. Scandinavian Journal of Medicine & Science in Sports, n/a-n/a.
YASUDA, T., FUKUMURA, K., IIDA, H. & NAKAJIMA, T. 2015. Effects of
detraining after blood flow-restricted low-load elastic band training on muscle
size and arterial stiffness in older women. SpringerPlus, 4.
YASUDA, T., FUKUMURA, K., SATO, Y., YAMASOBA, T. & NAKAJIMA, T.
2014a. Effects of detraining after blood flow-restricted low-intensity training on
muscle size and strength in older adults. Aging Clinical and Experimental
Research, 1-4.

308
YASUDA, T., LOENNEKE, J., OGASAWARA, R. & ABE, T. 2013. Influence of
continuous or intermittent blood flow restriction on muscle activation during
low-intensity multiple sets of resistance exercise. Acta Physiologica Hungarica,
100, 419-426.
YASUDA, T., LOENNEKE, J. P., OGASAWARA, R. & ABE, T. 2014b. Effects of
short-term detraining following blood flow restricted low-intensity training on
muscle size and strength. Clinical Physiology and Functional Imaging, n/a-n/a.
YASUDA, T., LOENNEKE, J. P., THIEBAUD, R. S. & ABE, T. 2012b. Effects of
Blood Flow Restricted Low-Intensity Concentric or Eccentric Training on
Muscle Size and Strength. PLoS One, 7, e52843.
YASUDA, T., LOENNEKE, J. P., THIEBAUD, R. S. & ABE, T. 2014c. Effects of
detraining after blood flow-restricted low-intensity concentric or eccentric
training on muscle size and strength. J Physiology Science.
YASUDA, T., OGASAWARA, R., SAKAMAKI, M., BEMBEN, M. G. & ABE, T.
2011. Relationship between limb and trunk muscle hypertrophy following high
intensity resistance training and blood flow restricted low intensity resistance
training. Clinical Physiology and Functional Imaging.
YASUDA, T., OGASAWARA, R., SAKAMAKI, M., OZAKI, H., SATO, Y. & ABE,
T. 2010c. Combined effects of low-intensity blood flow restriction training and
high-intensity resistance training on muscle strength and size. European Journal
of Applied Physiology, 1-9.
YOUNGER, A. S. E., MCEWEN, J. A. & INKPEN, K. 2004. Wide contoured thigh
cuffs and automated limb occlusion measurement allow lower tourniquet
pressures. Clinical Orthopaedics and Related Research, 428, 286.
ZANETTE, G., BONATO, C., POLO, A., TINAZZI, M., MANGANOTTI, P. &
FIASCHI, A. 1995. Long-lasting depression of motor-evoked potentials to
transcranial magnetic stimulation following exercise. Experimental Brain
Research, 107, 80-86.
ZIEMANN, U., CORWELL, B. & COHEN, L. G. 1998a. Modulation of plasticity in
human motor cortex after forearm ischemic nerve block. The Journal of
ZIEMANN, U., HALLETT, M. & COHEN, L. G. 1998b. Mechanisms of
deafferentation-induced plasticity in human motor cortex. The Journal of
ZIEMANN, U., ILIAC, T. V., PAULI, C., MEINTZSCHEL, F. & RUGE, D. 2004.
Learning modifies subsequent induction of long-term potentiation-like and long-
term depression-like plasticity in human motor cortex. The Journal of
ZIJDEWIND, I., BUTLER, J. E., GANDEVIA, S. C. & TAYLOR, J. L. 2006. The
origin of activity in the biceps brachii muscle during voluntary contractions of
the contralateral elbow flexor muscles. Experimental Brain Research, 175, 526-
535.

309
APPENDICIES
i. Plain Language Statement
ii. Strength and conditioning program

310
PLAIN LANGUAGE STATEMENT AND CONSENT FORM
TO: Participants
Plain Language Statement
Date:
Full Project Title: Neuromuscular and cardiovascular responses to blood flow
restriction resistance exercise
Principal Researcher: Dr Stuart Warmington
Associate Researcher(s): Dr Dawson Kidgell and Mr Chris Brandner
This Plain Language Statement and Consent Form is 15 pages long. Please make sure
you have all the pages.
1. Your Consent
You are invited to take part in this research project that is comprised of a series of
studies that form the basis of a PhD programme investigating light-load resistance
training combined with blood flow restriction (i.e. restricting blood flow to exercising
muscle), and the ability to use such training to improve clinical outcomes through
exercise. This Plain Language Statement contains detailed information about these
research studies in which you may be involved. Its purpose is to explain to you as
openly and clearly as possible all the procedures involved in these studies before you
decide whether or not to take part.
Please read this Plain Language Statement carefully. Feel free to ask questions about
any information in the document. You may also wish to discuss the project with a
relative or friend or your local health worker. Feel free to do this. Once you
understand what the project is about and if you agree to take part in a particular
study, you will be asked to sign the Consent Form. By signing the Consent Form, you
indicate that you understand the information and that you give your consent to

311
participate. You will be given a copy of the Plain Language Statement and Consent
Form to keep as a record.
2. Purpose and Background
Blood flow restriction (BFR) is a technique that involves reducing blood flow to muscle
during exercise training. This technique is used extensively in Japan where it is known
as Kaatsu. Briefly, this technique involves placing an inflatable pressure cuff around a
limb (i.e. arm/leg). The cuff is then inflated to a point where blood flow is reduced.
Once the cuff has been applied, subjects perform an exercise protocol at 20-50% of
their one repetition maximum for a high number of repetitions.
Recent evidence suggests that when light-load resistance training protocols are
combined with BFR, the gain in strength and muscle growth is similar to, or even
greater than, traditional heavy-load resistance exercise. However, the mechanisms
that contribute to this increase in strength following BFR are unclear.
Therefore, the purpose of this research is to investigate the effects of BFR-RT on the
acute responses and chronic adaptations of human neuromuscular, cardiovascular,
and metabolic systems. This project has important clinical implications for “at risk”
populations who require improved muscle strength, yet are not capable of resistance
training at a load that is typically required for strength development (i.e. using heavy-
loads). Such populations include people with musculoskeletal and neuromuscular
injury, metabolic diseases (such as obesity and diabetes), cardiac pathologies and the
elderly.
A total of approximately 120 people will participate in this project.
You are invited to participate in this research project because you are a healthy male
or female adult, aged 18-40 years, physically active (but not currently involved in
heavy-load resistance training), and free from musculoskeletal and neurological injury.
You have been provided with this Plain Language Statement and other medical forms,
and these need to be completed and returned before you may be formally accepted to
participate in a study. You will have been instructed about this process in your
correspondence with the researchers.

312
3. Study outlines
There are three studies in which you may participate. Each separate study is outlined
in sections 3.1 – 3.3. All three studies will involve an initial screening procedure to
ensure you are a suitable participant for the study. Additionally, all three studies will
follow similar pre- and post- testing methods to measure:
 Dynamic strength (i.e. lifting a resistance throughout a full range of motion; section
4.1)
 Isometric strength (i.e. contracting muscles as forcefully as possible, without
moving the joint; section 4.2), and
 Muscle thickness (section 4.3).
In all three studies, BFR will be combined with light-load resistance exercise. To restrict
muscle blood flow during light-load resistance training exercise, a compressive cuff will
be placed at the most upper portion of the arm (i.e. over the biceps muscle) and leg
(i.e. over the thigh; study 3 only) and inflated during exercise to a pressure
approximately 60% of your full arterial occlusion pressure, as measured painlessly via
limb occlusion pressure sensor. The final exercise pressure is approximately 70-150
mmHg, and is similar to the cuff pressure used by your GP when measuring your blood
pressure, and so you will most likely have experienced this process and the associated
sensations before. Upon completion of exercise the pressure cuff will immediately be
deflated.
3.1. Study 1
In study one participants will be required to attend a total of 4 testing sessions, each
separated by 7 days, over 4 weeks (see Table below). Visit one will be a familiarisation
session (approximately 30-60 minutes) where a number of pre-testing measurements
will be undertaken (see section 3.0). Additionally, testing of the central nervous system
(section 4.4) will also be performed in this study. You will then be required to
complete the following three testing sessions in a random order, one per week, over 4
weeks, whereby each session will require completion of a different exercise protocol
(according to the following table and as described below);

313
Session type No. of sessions Duration
Familiarisation 1 30-60 min
Heavy-load resistance exercise
session
1 60-90 min
Light-load resistance exercise
session
1 60-90 min
with blood flow restriction (LVO)
session
1 60-90 min
TOTAL 4 3.5 – 6 hours
3.1.1 Heavy-load resistance exercise session: You will be required to complete a
standard biceps curl with a dumbbell (right arm only) at 80% of your one-repetition
maximum (1-RM), with a repetition timing of 3 seconds on the up phase and 4 seconds
on the down phase. A total of 4 sets of 6-8 repetitions will be completed, separated by
3 minutes recovery. Prior to, and following the resistance exercise session, central
nervous system testing (section 4.5) will be performed.
3.1.2 Light-load resistance exercise session: You will be required to perform the same
standard biceps curl as described in section 3.1.1, however, the weight of the
dumbbell that will be used for exercise will be 20% of your 1-RM. A total of 4 sets will
be completed. In the first set a total of 30 repetitions will be completed, followed by 3
sets of 15 repetitions. The recovery period between sets will be 1 minute. Prior to, and
following the resistance exercise session, central nervous system testing (section 4.5)
will be performed.
3.1.3 Light-load resistance exercise with blood flow restriction session: You will be
required to perform the same exercise as described in section 3.1.2, however, during
exercise the most upper portion of the biceps will be occluded by an inflated pressure
cuff to a pressure of approximately 1.3 times your resting systolic blood pressure (140-
180 mmHg) for a duration no longer than 5 minutes at a time. The use of occlusion will
be applied during exercise only, therefore, pressure will be released at completion of
each exercise set. Prior to, and following the resistance exercise session, central
nervous system testing (section 4.5) will be performed.
3.2. Study 2

314
In study two participants will be required to attend a total of 4 testing sessions, each
separated by 7 days, over 4 weeks (see Table below). Visit one will be a familiarisation
session (approximately 30-60 minutes) where a number of pre-testing measurements
will be undertaken (see section 3.0). Additionally, cardiovascular testing (section 4.6)
will also be performed in this study. You will be required to complete the following
three testing in a random order, one per week, over 4 weeks, whereby each session
will require completion of a different exercise protocol (according to the following
table and described below);
Session type No. of sessions Duration
Familiarisation 1 30-60 min
Heavy-load resistance exercise
session
1 60-90 min
session
1 60-90 min
with blood flow restriction (LVO)
session
1 60-90 min
TOTAL 4 3.5 – 6 hours
For this study, exercise procedures will be identical to study 1 (see section 3.1.1 to
3.1.3). However, during exercise, and pre- and post- exercise, cardiovascular function
(section 4.6) will be assessed in all three session types.
3.3. Study 3
If you give your consent to participate in this project, you will be randomly allocated to
one of three resistance training groups, or to the ‘control’ group where you will be
required to complete all testing procedures, but will undertake no resistance training.
While study 1 and 2 involve elbow flexion exercise (i.e. a standard biceps curl), this
study will involve whole body resistance training made up of the following six
exercises: knee extension, squat, calf raise, bench press, seated row, and biceps curl.
The three resistance training groups are as follows:
3.3.1 Heavy-load resistance training: You will be required to exercise at 70% of your
one-repetition maximum (1-RM), with a repetition timing of 1.5 seconds on the up
phase and 1.5 seconds on the down phase. For the main outcome exercise (knee

315
extension) you will perform 4 sets of 8-10 repetitions, separated by 1 minute recovery
between sets. There is a 1 minute recovery period between each successive exercise,
where you will only be required to complete 3 sets of 8-10 repetitions with a 1 minute
recovery period between sets.
3.3.2 Light-load resistance exercise session: You will be required to perform the same
standard exercise protocol as described in section 3.3.1, however, the external load
during exercise that will be used will be 20% of your 1-RM. For the main outcome
exercise (knee extension), a total of 4 sets will be completed. In the first set a total of
30 repetitions will be completed, followed by 3 sets of 15 repetitions. The recovery
period between sets will be 30 seconds. There is a 1 minute recovery period between
each successive exercise, where you will only be required to complete 3 sets of 15
repetitions with a 30 second recovery period between sets.
3.3.3 Light-load resistance exercise with blood flow restriction session: You will be
required to perform the same exercise as described in section 3.3.2, however, during
exercise the most upper portion of your thigh and biceps will be restricted by an
inflated pressure cuff to a pressure of 60% of the total limb occlusion pressure which is
determined during familiarisation (approximately 70-150 mmHg). The restrictive cuff
will remain inflated until all 3 lower body exercises are completed first (approximately
15 mins), followed by a 5 minute rest period. The cuffs will then be attached and
inflated to the upper arm in order to complete 3 upper body exercises (approximately
15 mins).
If allocated to one of the above groups, you will be required to attend the laboratory
for a total of 20 supervised training sessions (approximately 45 minutes) over 10
weeks, three times per week on non consecutive days (i.e. Monday, Wednesday, and
Friday). In the week prior to commencement of training, visit one will be a
familiarisation session (approximately 60-90 minutes) where baseline pre-testing
measurements will be taken, these include;

316
 Dynamic strength (i.e. lifting a resistance throughout a full range of motion; section
4.1)
 Isometric strength (i.e. contracting muscles as forcefully as possible, without
moving the joint; section 4.2)
 Muscle thickness (section 4.3), and
 DEXA Whole body scan (section 4.4)
Following the first familiarisation session, a second testing session prior to training is
required whereby testing of the nervous system (section 4.5) and cardiovascular
system (section 4.6) will be performed.
Changes in muscle strength (section 4.1 & 4.2) and size (section 4.3 and 4.4) will be
examined prior to training, at the end of week 4 of the training program, and following
the training programme at week 8 (i.e. 3 testing sessions). In addition to this, central
nervous system (section 4.5), and cardiovascular testing (section 4.6) will be examined
at the same time points.
4 Testing procedures
4.1 Dynamic strength testing:
To measure muscle strength, the one-repetition maximum test (1-RM) will be
employed for all three studies. The 1-RM test is a measure of the maximal weight you
can lift with one repetition, throughout a full range of motion. You will be asked what
you believe your 1-RM strength to be, and this load will serve as your starting point. If
you successfully lift one repetition, the weight of the dumbbell will be increased for
the next single repetition attempt. 1-RM testing will continue until you can no longer
lift the selected weight. Your 1-RM will be the heaviest weight that you successfully lift
with good technique. You will be given period of 3 min rest between attempts to
minimise the development of muscle fatigue.
4.2 Isometric strength:
Three maximal isometric contractions (i.e. contracting muscles as forcefully as
possible, without moving the joint) will be performed using a dynamometer (Biodex
System 4 Pro, Biodex Medical Systems, Shirley USA) to measure your maximal

317
isometric strength. This will require you to perform three contractions while seated at
the dynamometer machine, pressing against the machine, which will hold your limb in
a stable position and prevent joint movement while you contract as forcefully as
possible for 5 seconds. You will be given a 90 second rest period between each
contraction to allow optimal performance. All three studies will require testing of the
biceps.
4.3 Ultrasound testing for muscle size:
Ultrasonic images will be performed to measure any changes in muscle size. An
ultrasound transducer will be placed lightly on the skin of the muscle of interest, with
the muscles relaxed. Sound waves will penetrate into the muscle, and generate an
image that will be used to determine muscle thickness. This process is safe, painless
and used commonly in a clinical setting to view internal structures without any ill
effects. Ultrasound images will be taken at the following 7 sites: biceps, tricep,
pectoralis major (chest), subscapularis (back), quadricep, hamstring, and calf.
4.4 DEXA scan:
Prior to the scan, your weight, height, waist and hip circumference will be measured.
The scan measures ‘body composition,’ or the fat and lean (non‐fat tissue such as bone
and muscle) mass of your body and indicates where your fat is mainly stored (ie.
abdomen/trunk, arms and legs). You will be asked to lie still on a table while the scan
is being done. The scan will usually take less than 10 minutes.
4.5 Central nervous system testing:
Measurement of central nervous system excitability is conducted using a paired-pulse
transcranial magnetic stimulation (TMS) system. A Bi-stim 2002
paired-pulse stimulator
will be used to stimulate the nerve tissue of your brain. TMS is a non-invasive, painless
and safe technique that has been in use world-wide in clinical, and laboratory settings,
for more than 25 years, and is used routinely to investigate the function of the nervous
system with very low risk. The Bi-stim is comprises of two stimulators with a “figure of
8” stimulator coil (Figure 1a). The coil is held over the scalp by the investigator and two
brief magnetic pulses flow through the coil (Figure 1b). These in turn activates the
brain tissue beneath the coil. From your perspective, all you will notice is possibly two
light taps on the head (not all participants report this) and an audible clicking sound.

318
Each tap is a very low stimulus that activates nerve cells in your brain directly, resulting
in a small contraction of the biceps muscle and slight movement of the arm. So, when
the coil is held over the region of the brain that makes us move (i.e. the motor cortex)
the effects of stimulation can be measured by recording responses produced in the
biceps muscle of the arm, and quadriceps muscle of the thigh. These responses are
recorded with special electrodes (electromyography [EMG] pads) taped to the skin
overlying the biceps muscles, and therefore reflects the level of activity in the brain
and spinal cord that is associated with that muscle.
Figure. 1a. Paired- pulse Magstim 2002
stimulator Figure. 1b.Participant with Magstim coil placement
4.6 Cardiovascular testing:
During the testing sessions where cardiovascular variables will be measured you will
be required to wear a small face mask or mouthpiece to breathe through so that
expired gasses can be collected and analysed. The researchers will fit you with the
mask and it will in no-way impair your ability to breathe. At all times you will be
breathing normal room air.
There is one exception, and that is when performing a particular breathing manoeuvre
that enables the measurement of some heart function parameters. During this
manoeuvre, you will be rebreathing a special gas mixture from a bag connected to
your mouthpiece. You will be instructed on how to perform this manoeuvre, and the
researchers will guide you through this manoeuvre each time it is necessary. The
manoeuvre requires little effort other than for you to concentrate on the depth and
timing of your breathing. This mavourve is quite safe, and you cannot taste the gas
mixture, so it will seem like you are breathing normal air. Principally this is because the
special gas mixture is 90% air.

319
In addition, blood pressure will be measured at regular points during a testing session.
This will require placing a blood pressure cuff around the upper arm that will be
inflated via an automated blood pressure monitor unit. It is expected that you will be
familiar with having your blood pressure measured as this is a standard clinical
measurement taken on a regular basis by your GP.
5 Possible Benefits
There are no direct benefits from participation in this project. However, your
participation throughout this study will provide important and valuable information
regarding the benefits of resistance training on strength development and neural
excitability, as well as cardiovascular function, which may go on to benefit the wider
community by assisting with the development of enhanced rehabilitation programs or
exercise performance.
6 Possible Risks
There are no foreseeable medical risks to participation in this project. However,
various factors may exclude you from participating in these studies, and they are
detailed below. You have the right to terminate testing or withdraw from the study at
any time without adverse consequences to yourself or this study, in which case any
information obtained from you will not be used further.
Testing of the central nervous system (section 4.4) is painless and safe. However,
participants may experience discomforts on the scalp musculature, which is similar to being
tapped lightly on the head with a finger. When using paired-pulse TMS to test the central
nervous system, magnetism is used. Therefore, various factors that may exclude you from
participating in these studies. These include having a pacemaker or metal objects like
cerebral aneurysm clips inside your body. Prior to being accepted into a study you will be
asked a series of questions in the “TMS adult safety screen” document to determine if there
are any factors that may exclude you from participating.
The resistance training program and functional strength testing, involve risks of muscle
soreness and stiffness, although this is unlikely due to the type of muscular
contractions contained in the program and testing. The BFR pressure (80-120 mmHg)

320
has not been shown to result in any deleterious acute or chronic effects. However, you
may experience slight discomfort or numbness of the upper and lower limbs during
exercise, similar to the feeling of pins and needles. There is little knowledge of the
effect of BFR-RE on the cardiovascular system. These include those with bleeding
disorders or on anticoagulants. Therefore, those with compromised cardiac health will
be excluded from these studies. Prior to being accepted into these studies you will be
asked a series of questions in the “Adult pre-exercise screening tool” document to
determine if there are any factors which may stop you from participating in this study.
This research study involves exposure to a very small amount of radiation from DEXA
scans of your body. As part of everyday living, everyone is exposed to naturally
occurring background radiation and receives a dose of about 2 millisieverts (mSv) each
year. The effective dose you will receive from all four (4) DEXA scans of your body will
be approximately 0.04 mSv. At these dose levels, no harmful effects of radiation have
been demonstrated, as any effect is too small to measure. The risk is believed to be
very low.
If you have been involved in any other research studies that involve radiation, please
inform us. Please keep this Patient Information and Consent Form that includes
information about your exposure to radiation in this study for at least five years. You
will be required to provide this information to researchers of any future research
studies involving exposure to radiation
The risks involved in this project are minimal because experienced staff will be
conducting the tests using standard procedures. The current research on BFR training
with respect to safety outcomes confirms that BFR, when used in a controlled
environment by trained and experienced personell, provides a safe training alternative
to most individuals regardless of age and training status.
7 Privacy, Confidentiality and Disclosure of Information
Any personal information provided by you to the researchers involved with this project
will remain confidential. It will only be disclosed with your permission, subject to legal
requirements. All individual results will remain strictly confidential and no names will
be used in any publications.

321
It is the intention of the researchers to publish the results of this project. In such
circumstances your identity will not be disclosed. In all cases, information will be
provided in such a way that you cannot be identified. In addition, any information
collected will be coded and de-identified, and stored securely in electronic format
where only the researchers will have access to the data.
The results of this project will be discussed at national and or international
conferences. In all cases your identity and personal information will not be disclosed.
Information will be provided in such a way that you cannot be identified.
The Deakin University Human Research Ethics Committee requires that all material
must be kept for a minimum of 6 years to allow reference to interest and discussion.
After a period of six years from the date of publication of public release of the work of
the research, paper copies of the subject's individual responses will be disposed of in
the interests of limiting physical space taken up by the records. Electronic copies of all
data will be retained indefinitely.
8 New Information Arising During the Project
Although unlikely, during the research project, new information about the risks and
benefits of the project may become known to the researchers. If this occurs, you will
be told about this new information. This new information may mean that you can no
longer participate in this research.
Similarly, as you will be monitored during each testing and training session, if it
appears for any reason that you or the research staff are at risk by your continuing
participation in the testing or training session, the person(s) supervising the research
will stop your participation. In all cases, you will be offered all available care to suit
your needs and medical condition.
9 Results of Project
Upon completion of the project it is anticipated that the results will be submitted for
potential peer-review and journal publication in the field of exercise science. The
results may also be presented orally to a scientific meeting in Australia or
internationally. Participants that would like copies of published material arising from
the project should request this from the principle researcher (see section 13) at the

322
conclusion of the project. All participants will be notified if the project is accepted for
publication.
10 Participation is Voluntary
Participation in any research project is voluntary. If you do not wish to take part you
are not obliged to. If you decide to take part and later change your mind, you are free
to withdraw from the project at any stage. Any information obtained from you to date
will not be used and will be destroyed.
Your decision whether to take part or not to take part, or to take part and then
withdraw, will not affect your relationship with Deakin University.
Before you make your decision, a member of the research team will be available to
answer any questions you have about the research project. You can ask for any
information you want. Sign the Consent Form only after you have had a chance to ask
your questions and have received satisfactory answers.
If you decide to withdraw from this project, please notify a member of the research
team or complete and return the Revocation of Consent Form attached. This notice
will allow the research team to inform you if there are any health risks or special
requirements linked to withdrawing.
11 Ethical Guidelines
This project will be carried out according to the National Statement on Ethical Conduct
in Human Research (2007) produced by the National Health and Medical Research
Council of Australia. This statement has been developed to protect the interests of
people who agree to participate in human research studies. The ethical aspects of this
research project have been approved by the Human Research Ethics Committee of
Deakin University under project 2011-228.
12 Reimbursement for your costs
You will not be paid for your participation in this project.

323
13 Complaints
If you have any complaints about any aspect of the project, the way it is being
conducted or any questions about your rights as a research participant, then you may
contact:
The Manager, Office of Research Integrity, Deakin University, 221 Burwood Hwy,
Burwood, VIC 3125, Telephone: (03) 9251 7129, Facsimile: 9244 6581; research-
ethics@deakin.edu.au. Please quote this project number [2011-228].
14 Further Information, Queries or Any Problems
If you require further information, wish to withdraw your participation or if you have
any problems concerning this project (for example, any side effects), you can contact
the principal researcher. The researchers responsible for this project are:
Principal Researcher:
Dr Stuart Warmington
School of Exercise and
Nutrition Sciences
Deakin University
221 Burwood Hwy, Burwood,
VIC 3125
Telephone: +61 3 9251 7013
Fax: +61 3 9244 6017
Email:
stuart.warmington@deakin.e
du.au
Principal Researcher:
Dr Dawson Kidgell Centre for Physical Activity an
Nutrition Sciences
Deakin University
VIC 3125
Telephone: +61 3 9251 7264
Fax: +61 3 9244 6017
Email:
dawson.kidgell@deakin.edu.
au
Student Researcher:
Mr Chris Brandner
Nutrition Sciences
Deakin University
VIC 3125
Telephone: +61 3 9251 7783
Mobile: 0422 117 274
Email:
c.brandner@deakin.edu.au

324
TO: Participant
Consent Form
Date:
Full Project Title:
Reference Number:
I have read and I understand the attached Plain Language Statement.
I freely agree to participate in this project according to the conditions in the Plain
Language Statement.
I have been given a copy of the Plain Language Statement and Consent Form to keep.
The researcher has agreed not to reveal my identity and personal details, including
where information about this project is published, or presented in any public form.
Chosen study(s) .............................................................................................
Participant’s Name (printed) ……………………………………………………………………
Signature ……………………………………………………… Date ……………………...
Please mail this form to:
Deakin University
221 Burwood Hwy, Burwood, VIC 3125
Telephone: +61 3 9251 7013
Fax: +61 3 9244 6017
Email: stuart.warmington@deakin.edu.au

325
TO: Participant
Revocation of Consent Form
(To be used for participants who wish to withdraw from the project)
Date:
Full Project Title:
Reference Number:
I hereby wish to WITHDRAW my consent to participate in the above research project
and understand that such withdrawal WILL NOT jeopardise my relationship with
Deakin University
Chosen study(s) .............................................................................................
Participant’s Name (printed) …………………………………………………….................
Signature ………………………………………………………………. Date ……………………
Please mail this form to:
Deakin University
221 Burwood Hwy, Burwood, VIC 3125
Telephone: +61 3 9251 7013
Fax: +61 3 9244 6017
Email: stuart.warmington@deakin.edu.au

Thesis final v1 2015 - for print 2016

More Related Content

What's hot (20)

Viewers also liked (8)

Similar to Thesis final v1 2015 - for print 2016 (20)

Thesis final v1 2015 - for print 2016