DISTRIBUTION, MORPHOLOGY, AND NEUROCHEMISTRY OF ENDOCARDIAL AND EPICARDIAL NERVE-TERMINAL ARBORIZATIONS IN THE HUMAN HEART

Background The heart contains a variety of morphologically distinct ne rve terminals known to influence cardiac function. Little is known abo ut the distribution, morphology, and neurochemistry of these terminals in the human heart. Methods and Results We examined the entire endoca rdial and epicardial surfaces of infant and adult hearts obtained post mortem and at transplantation using immunohistochemical and histochemi cal staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diam eter, 6 to 10 mu m) immunoreactive for myelin basic protein were ident ified in the atrial endocardium, epicardium, and coronary sinus, and f our types were distinguished by differences in immunostained nerve are a (range, 358 to 797 mu m(2)) and dispersion (range, 620 to 4684 mu m( 2)). These terminals displayed immunoreactivity for tyrosine hydroxyla se, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in <5% of endo cardial terminals and in no epicardial terminals arising from myelinat ed fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be ass ociated with local ganglia. A distinct population of terminals (mean s tained area, 35 mu m(2); 18 to 53 mu m(2), 95% CI; and mean dispersion , 59 mu m(2); 38 to 80 mu m(2), 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 mu m; 2.2 to 2.8 mu m, 95% C I) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. Conclusions Specialized nerve terminals a re 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, suggestin g that acetylcholine, catecholamines, and neuropeptide Y may be presen t in sensory acid autonomic nerves in the human heart.