Cholinergic innervation of the canine and human ventricular conducting system. Anatomic and electrophysiologic correlations.

Augmentation of vagal tone increases ventricular fibrillation threshold (VFT) under nonischemic and ischemic conditions and protects against spontaneous ventricular fibrillation during experimental myocardial infarction. The purpose of this study was to identify the anatomic pathways responsible for this cholinergically-mediated enhanced electrical stability and to determine whether or not these pathways are present in human hearts. Rich cholinergic innervation of the sinoatrial node, atrioventricular node, and atrial myocardium was confirmed in both canine and human hearts. Although sparse cholinergic innervation was present in ventricular myocardium, numerous cholinergic nerve fibers were present in ventricular conduction tissue of both canine and human hearts. To determine whether these cholinergic fibers mediate the protective effects of vagal stimulation, cholinergic fibers to the ventricular conducting system were ablated in dogs. The ablation procedures used resulted in histologic absence of cholinergic nerves in the ventricular conducting system; innervation of the atrium, however, was histologically intact. In these animals vagal stimulation no longer increased VFT but still caused slowing of the sinus rate. The effect of vagal stimulation on VFT was shown to be independent of adrenergic innervation in a group of catecholamine depleted animals (6-hydroxydopamine). We conclude that 1) the enhanced ventricular electrical stability produced by vagal stimulation in dogs is mediated by cholinergic nerve fibers which supply the ventricular conduction system, and 2) this anatomic pathway is present in human hearts.