DEVELOPMENT OF THE PEPTIDERGIC INNERVATION OF HUMAN HEART

The aim of the present investigation was to study the developing pepti dergic innervation of the human fetal heart of 7-24 wk gestational age . An immunohistochemical approach was adopted and the total innervatio n visualised with antisera to general neuronal and Schwann cell marker s, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NP Y), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immuno reactive nerves were not observed until the 10th week of gestation. NP Y-immunoreactive nerve fibres constituted the major subpopulation of p eptide-containing nerves identified in the fetal heart, exhibiting a d escending atrial to ventricular density gradient, and were first ident ified during the 10th wk of gestation. Somatostatin- and VIP-immunorea ctive nerves appeared at 10-12 wk of gestation and were mainly distrib uted in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other p eptide-containing nerves appear to be of extrinsic origin, including t hose immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathe tic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreacti vity, were demonstrated before the adrenergic innervation has previous ly been shown to be present by formaldehyde-induced fluorescence stain ing of catecholamines. The onset of the CGRP- and SP-immunoreactive in nervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent inner vation occurs later than the autonomic. The differential appearance an d distribution of peptide-containing nerve subpopulations indicate tha t there is a chronological order to the development of the autonomic a nd sensory components of human cardiac innervation.