Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is im portant for the control of cardiac dynamics, especially in the conduction s ystem. Our objective was to assess the relative distribution of autonomic n erves in the pig heart, focusing initially on the conduction system but add ressing also the myocardium, endocardium and epicardium (see Crick et aI. 1 999). Quantitative immunohistochemical and histochemical techniques were ad opted. All regions of the conduction system possessed a significantly highe r relative density of the total neural population immunoreactive for the ge neral neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjac ent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventr icular node, and the penetrating atrioventricular bundle. A differential pa ttern of PGP 9.5-immunoreactive innervation was present within the atrioven tricular node and between the components of the ventricular conduction tiss ues, the latter being formed by an intricate network of Purkinje fibres. Nu merous ganglion cell bodies were present in the peripheral regions of the s inus node, in the tissues of the atrioventricular groove, and even in the i nterstices of the compact atrioventricular node. Acetylcholinesterase (AChE )-containing nerves were the dominant subpopulation observed, representing 60-70 % of the total pattern of innervation in the nodal tissues and penetr ating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive ner ves were the next most abundant neural subpopulation, representing 37 % of the total pattern of innervation in the compact atrioventricular node compa red with 25 % in the transitional nodal region. A minor population of gangl ion cell bodies within the atrioventricular nodal region displayed TH immun oreactivity. The dominant peptidergic nerve supply possessed immunoreactivi ty for neuropeptide Y (NPY), which displayed a similar pattern of distribut ion to that of TH-immunoreactive nerve fibres. Calcitonin gene-related pept ide (CGRP)immunoreactive nerves represented 8-9 % of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14-19 % in the bundle branches. Somatostatin-immunoreactive nerve fibres w ere relatively sparse (4-13% of total innervation) and were most abundant i n the nodes, especially the compact atrioventricular node. The total patter n of innervation of the porcine conduction system was relatively homogeneou s. A substantial proportion of nerve fibres innervating the nodal tissues c ould be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular condu ction tissues was similar to that observed in the bovine heart, but markedl y different to that of the human heart. It is important that we are aware o f these findings in view of the future use of transgenic pig hearts in huma n xenotransplantation.