Human endocardial innervation and its relationship to the endothelium: an immunohistochemical, histochemical, and quantitative study.

The endocardium contains an extensive neural plexus, the composition and function of which are unclear. The aim of this study was to characterise the innervation of the endocardium in terms of the relative density and distribution of its autonomic and sensory nerve subpopulations and to assess the relationship between these nerves and endocardial endothelial cells. Immunohistochemical, histochemical, confocal, and quantitative image processing techniques were applied to whole mount preparations of human postmortem endocardium obtained within 24 h of death. The overall distribution of nerve fibres and fascicles was demonstrated using antisera to the general neural marker protein gene product 9.5 (PGP 9.5). Nerves displaying acetylcholinesterase activity represented the main nerve subpopulation, occupying 9-18% of the quantified field area. Neuropeptide Y immunoreactive nerves formed the most numerous peptide containing nerve subpopulation identified, occupying 5-19% and 2-7% of the field area in the ventricle and atrial endocardium respectively and having similar distribution patterns to tyrosine hydroxylase immunoreactive nerves. Nerves showing immunoreactivity for somatostatin, vasoactive intestinal polypeptide, and substance P were detected at a lower density, occurred more frequently in the ventricular than atrial endocardium, and showed a similar distribution in the right and left sides of the heart. Combined peptide immunofluorescence and acetylcholinesterase staining, of the same preparation, indicated that putative sympathetic and sensory nerve subpopulations could be distinguished from presumed parasympathetic, acetylcholinesterase positive, nerves. The relationship between immunostained nerves and endothelial cells was assessed using confocal microscopy. Varicose nerve fibres were detected within 0.2 micron of overlying endothelial cells in the right ventricle and between 0.4-0.6 micron in the left ventricle. The heterogeneous population of nerve fibres demonstrated in the human endocardium may influence the known interaction between endocardial endothelial cells and the myocardium.