Inside the Cardiac Brain: How are Pigs Wired

Porcine hearts are a mainstay in cardiovascular research, often praised for their anatomical and physiological similarities to human hearts. But when we look beneath the surface—into the intricate web of the epicardiac nerve plexus (ENP) — a more nuanced and fascinating story unfolds. Understanding these differences is not just a matter of anatomy; it’s essential for anyone developing therapies that interact with the cardiac nervous system. 🧬⚙️

In the human heart, the intrinsic innervation follows a relatively well-defined structure. The right atrium is innervated by two subplexuses, the left atrium by three, the right ventricle by one, and the left ventricle by three subplexuses. 🫀 The epicardiac ganglia are most densely concentrated near the heart hilum, particularly on the dorsal and dorsolateral surfaces of the left atrium—regions where up to 50% of all cardiac ganglia are found. On average, the human heart houses about 836 epicardiac ganglia and an estimated 43,000 intrinsic neurons. These ganglia are primarily accessed via nerves entering around the aorta and pulmonary trunk, routes also seen in canine hearts. 🧠🐶

The porcine heart, however, follows a different architectural logic. Neural inputs enter the heart at five distinct sites, most notably around the superior vena cava and the left azygos vein—a structure absent in humans. 🐷 This makes the porcine heart a unique case: it lacks the dense neural inputs around the aorta and pulmonary trunk that are typical in humans. In pigs, these major access points supply four subplexuses to the left atrium, three to the left ventricle, and two each to the right atrium and ventricle.

What’s also fascinating is how the epicardiac ganglia in pigs are widely dispersed across numerous discrete sites throughout the atria, in contrast to the more clustered organization in humans. The ventricles, in turn, host fewer ganglia, which are mostly located near the coronary groove. The porcine heart contains around 362 ganglia and approximately 12,000 intrinsic neurons—fewer than humans, but forming a unique and complex network nonetheless.

So what does this mean for translational research? ⚠️ If you're developing therapies targeting arrhythmias, autonomic modulation, or cardiac neurointerfaces, assuming equivalence between species could lead to critical missteps. The pig remains an incredibly valuable model—but only when we acknowledge its unique cardiac brain. 🧠🫀

As we push the boundaries of bioelectronic medicine and cardiovascular innovation, one thing is clear: not all hearts are wired the same.

📚 References

Pauza DH, Skripka V, Pauziene N, Stropus R. Morphology, distribution and variability of the epicardiac neural ganglionated subplexuses in the human heart. Anat Rec. 2000;259(4):353–382.

Batulevicius D, Skripka V, Pauziene N, Pauza DH. Topography of the porcine epicardiac nerve plexus as revealed by histochemistry for acetylcholinesterase. Auton Neurosci. 2008;138(1–2):64–75.

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