Distribution, Morphology, and Neurochemistry of Endocardial and Epicardial Nerve Terminal Arborizations in the Human Heart

Abstract

Background The heart contains a variety of morphologically distinct nerve terminals known to influence cardiac function. Little is known about the distribution, morphology, and neurochemistry of these terminals in the human heart. Methods and Results We examined the entire endocardial and epicardial surfaces of infant and adult hearts obtained postmortem and at transplantation using immunohistochemical and histochemical staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diameter, 6 to 10 μm) immunoreactive for myelin basic protein were identified in the atrial endocardium, epicardium, and coronary sinus, and four types were distinguished by differences in immunostained nerve area (range, 358 to 797 μm 2 ) and dispersion (range, 620 to 4684 μm 2 ). These terminals displayed immunoreactivity for tyrosine hydroxylase, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in <5% of endocardial terminals and in no epicardial terminals arising from myelinated fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be associated with local ganglia. A distinct population of terminals (mean stained area, 35 μm 2 ; 18 to 53 μm 2 , 95% CI; and mean dispersion, 59 μm 2 ; 38 to 80 μm 2 , 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 μm; 2.2 to 2.8 μm, 95% CI) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. Conclusions Specialized nerve terminals are distributed more widely in the human heart than has been described in experimental animals. These terminals express either AChE activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity, suggesting that acetylcholine, catecholamines, and neuropeptide Y may be present in sensory and autonomic nerves in the human heart.