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Concomitant with the development of surgical treatment of cardiac arrythmias and management of myocardial ischemia, there is renewed interest in morphology of the intrinsic cardiac nervous system. In this study, we analyze the topography and structure of the human epicardiac neural plexus (ENP) as a system of seven ganglionated subplexuses. The morphology of the ENP was revealed by a histochemical method for acetylcholinesterase in whole hearts of 21 humans and examined by stereoscopic, contact, and bright-field microscopy. According to criteria established to distinguish ganglionated subplexuses, they are epicardiac extensions of mediastinal nerves entering the heart through discrete sites of the heart hilum and proceeding separately into regions of innervation by seven pathways, on the courses of which epicardiac ganglia, as wide ganglionated fields, are plentifully located. It was established that topography of epicardiac subplexuses was consistent from heart to heart. In general, the human right atrium was innervated by two subplexuses, the left atrium by three, the right ventricle by one, and the left ventricle by three subplexuses. The highest density of epicardiac ganglia was identified near the heart hilum, especially on the dorsal and dorsolateral surfaces of the left atrium, where up to 50% of all cardiac ganglia were located. The number of epicardiac ganglia identified for the human hearts in this study ranged from 706 up to 1,560 and was not correlated with age in most heart regions. The human heart contained on average 836 +/- 76 epicardiac ganglia. The structural organization of ganglia and nerves within subplexuses was observed to vary considerably from heart to heart and in relation to age. The number of neurons identified for any epicardiac ganglion was significantly fewer in aged human compared with infants. By estimating the number of neurons within epicardiac ganglia and relating this to the number of ganglia in the human epicardium, it was calculated that approximately 43,000 intrinsic neurons might be present in the ENP in adult hearts and 94,000 neurons in young hearts (fetuses, neonates, and children). In conclusion, this study demonstrates the total ENP in humans using staining for acetylcholinesterase, and provides a morphological framework for an understanding of how intrinsic ganglia and nerves are structurally organized within the human heart.

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The aim of the present study was to elucidate the topography and architecture of the intrinsic neural plexus (INP) in the canine right atrium because of its importance for selective denervation of the sinoatrial node (SAN). The morphology of the intrinsic INP was revealed by a histochemical method for acetylcholinesterase in whole hearts of 36 mongrel dogs and examined by stereoscopic, contact, and electron microscopes. At the hilum of the heart, nerves forming a right atrial INP were detected in five sites adjacent to the right superior pulmonary veins and superior vena cava (SVC). Nerves entered the epicardium and formed a INP, the ganglia of which, as a wide ganglionated field, were continuously distributed on the sides of the root of the SVC (RSVC). The epicardiac ganglia located on the RSVC were differentially involved in the innervation of the sinoatrial node, as revealed by epicardiac nerves emanating from its lower ganglia that proceed also into the atrial walls and right auricle. The INP on the RSVC (INP-RSVC) varied from animal to animal and in relation to the age of the animal. The INP-RSVC of juvenile dogs contained more small ganglia than that of adult animals. Generally, the canine INP-RSVC included 434+/-29 small, 17+/-4 medium-sized, and 3+/-1 large epicardiac ganglia that contained an estimated 44,700, 6,400, and 2,800 neurons, respectively. Therefore, the canine right atrium, including the SAN, may be innervated by more than 54,000 intracardiac neurons residing mostly in the INP-RSVC. In conclusion, the present study indicates that epicardiac ganglia that project to the SA-node are distributed more widely and are more abundant than was previously thought. Therefore, both selective and total denervation of the canine SAN should involve the whole region of the RSVC containing the INP-RSVC.

Since many human heart diseases involve both the intrinsic cardiac neurons and nerves, their detailed normal ultrastructure was examined in material from autopsy cases without cardiac complications obtained no more than 8 h after death. Many intracardiac nerves were covered by epineurium, the thickness of which was related to nerve diameter. The perineurial sheath varied from nerve to nerve and, depending on nerve diameter, contained up to 12 layers of perineurial cells. The sheaths of the intracardiac nerves therefore become progressively attenuated during their course in the heart. The intraneural capillaries of the human heart differ from those in animals in possessing an increased number of endothelial cells. A proportion of the intraneural capillaries were fenestrated. The number of unmyelinated axons within unmyelinated nerve fibres was related to nerve diameter, thin cardiac nerves possessing fewer axons. The most distinctive feature was the presence of stacks of laminated Schwann cell processes unassociated with axons that were more frequent in older subjects. Most unmyelinated and myelinated nerve fibres showed normal ultrastructure, although a number of profiles displayed a variety of different axoplasmic contents. Collectively, the data provide baseline information on the normal structure of intracardiac nerves in healthy humans which may be useful for assessing the degree of nerve damage both in autonomic and sensory neuropathies in the human heart.Key words : Intracardiac nervous system ; peripheral nervous system ; vasculature. The pivotal significance of the intracardiac nervous system in influencing cardiac rate, atrial and ventricular refractoriness, coronary artery blood flow, valvular function and atrial natriuretic peptide secretion, as well as in causing the development of hazardous disorders of human cardiac activity, has been established in a range of studies (Forssmann,