Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension.

Persistent arterial hypertension initiates cardiac autonomic imbalance and alters cardiac tissues. Previous studies have shown that neural component contributes to arterial hypertension etiology, maintenance, and progression and leads to brain damage, peripheral neuropathy, and remodeling of intrinsic cardiac neural plexus. Recently, significant structural changes of the intracardiac neural plexus were demonstrated in young prehypertensive and adult hypertensive spontaneously hypertensive rats (SHR), yet structural alterations of intracardiac neural plexus that occur in the aged SHR remain undetermined. Thus, we analyzed the impact of uncontrolled arterial hypertension in old (48-52 weeks) SHR and the age-matched Wistar-Kyoto rats (WKY). Intrinsic cardiac neural plexus was examined using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in cardiac sections and whole-mount preparations. Our findings demonstrate that structural changes of intrinsic cardiac neural plexus caused by arterial hypertension are heterogeneous and may support recent physiological implications about cardiac denervation occurring together with the hyperinnervation of the SHR heart. We conclude that arterial hypertension leads to (i) the decrease of the neuronal body area, the thickness of atrial nerves, the number of myelinated nerve fibers, unmyelinated axon area and cumulative axon area in the nerve, and the density of myocardial nerve fibers, and (ii) the increase in myelinated nerve fiber area and density of neuronal bodies within epicardiac ganglia. Despite neuropathic alterations of myelinated fibers were exposed within intracardiac nerves of both groups, SHR and WKY, we consider that the determined significant changes in structure of intrinsic cardiac neural plexus were predisposed by arterial hypertension.

Comparative gross anatomy of epicardiac ganglionated nerve plexi on the human and sheep cardiac ventricles.

This study aimed to examine the distribution and quantitative parameters of the epicardiac ventricular neural ganglionated plexus in the hearts of humans and sheep, highlighting the differences of this plexus in humans and large models. Five non-sectioned pressure distended whole hearts of the human newborns and 10 hearts of newborn German black-faced lambs were investigated applying a histochemical method for acetylcholinesterase to stain epicardiac neural structures with their subsequent stereomicroscopic examination. In humans, the ventricular nerves are spread by four epicardiac nerve subplexuses, that is, the left and right coronary as well as the left and middle dorsal. In sheep, the ventricular nerves are spread by five epicardiac nerve subplexuses, that is, the left and right coronary, the left and middle dorsal and the right ventral ones. The ventricular epicardium involved up to 129 ganglia in humans and up to 198-in sheep. The largest number of the ventricular ganglionic cells in humans were located on the ventral side, in front of the conus arteriosus, while on sheep ventricles, the most numerous neurons distributed on the dorsal wall of the left ventricle. This comparative study of the morphological patterns of the human and sheep ventricles demonstrates that the sheep heart is neuroanatomically distinct from the human one and this must be taking into consideration using the sheep model for the heart physiology experiments.

Early structural alterations of intrinsic cardiac ganglionated plexus in spontaneously hypertensive rats.

Persistent arterial hypertension leads to structural and functional remodeling of the heart resulting in myocardial ischemia, fibrosis, hypertrophy, and eventually heart failure. Previous studies have shown that individual neurons composing the intracardiac ganglia are hypertrophied in the failing human, dog, and rat hearts, indicating that this process involves changes in cardiac innervation. However, despite a wealth of data on changes in intrinsic cardiac ganglionated plexus (GP) in late-stage disease models, little is known about the effects of hypertension on cardiac innervation during the early onset of heart failure development. Thus, we examined the impact of early hypertension on the structural organization of the intrinsic cardiac ganglionated plexus in juvenile (8-9 weeks) and adult (12-18 weeks) spontaneously hypertensive (SH) and age-matched Wistar-Kyoto (WKY) rats. GP was studied using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in whole-mount preparations and tissue sections. Here, we report intrinsic cardiac GP of SH rats to display multiple structural alterations: (i) a decrease in the intracardiac neuronal number, (ii) a marked reduction in axonal diameters and their proportion within intracardiac nerves, (iii) an increased density of myocardial nerve fibers, and (iv) neuropathic abnormalities in cardiac glial cells. These findings represent early neurological changes of the intrinsic ganglionated plexus of the heart introduced by early-onset arterial hypertension in young adult SH rats.

Neuroanatomy of the Pig Cardiac Ventricles. A Stereomicroscopic, Confocal and Electron Microscope Study.

Although the pig is a model for heart disease, the neuroanatomy of cardiac ventricles (CV) in this species remains undetailed. We aimed to define the innervation pattern of pig CV, combining histochemistry for acetylcholinesterase, immunofluorescent labeling and electron microscopy. Forty nine examined pig hearts show that the major nerves supplying the ventral side of CV descend from the venous part of the heart hilum. Fewer in number and smaller in size, epicardial nerves supply the dorsal half of the CV. Epicardial nerves on the left ventricle are thicker than those on the right. Ventricular ganglia of various sizes distribute at the basal level of both CV. Averagely, we found 3,848 ventricular neuronal somata per heart. The majority of somata were cholinergic, although ganglionic cells of different neurochemical phenotypes (positive for nNOS, ChAT/nNOS, or ChAT/TH) were also observed. Large and most numerous nerves proceeded within the epicardium. Most of endocardium and myocardium contained a network of nerve bundles and nerve fibers (NFs). But, a large number of thin nerves extended along the bundle of His and its branches. The majority of NFs were adrenergic, while cholinergic NFs were scarce yet more abundant than nitrergic ones. Sensory NFs positive for CGRP were the second most abundant phenotype after adrenergic NFs in all layers of the ventricular wall. Electron microscopy elucidated that ultrastructure of nerves varied between different areas of CV. The described structural organization of CV provides an anatomical basis for further functional and pathophysiological studies in the pig heart. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1756-1780, 2017. © 2017 Wiley Periodicals, Inc.

Innervation of the rabbit cardiac ventricles.

The rabbit is widely used in experimental cardiac physiology, but the neuroanatomy of the rabbit heart remains insufficiently examined. This study aimed to ascertain the architecture of the intrinsic nerve plexus in the walls and septum of rabbit cardiac ventricles. In 51 rabbit hearts, a combined approach involving: (i) histochemical acetylcholinesterase staining of intrinsic neural structures in total cardiac ventricles; (ii) immunofluorescent labelling of intrinsic nerves, nerve fibres (NFs) and neuronal somata (NS); and (iii) transmission electron microscopy of intrinsic ventricular nerves and NFs was used. Mediastinal nerves access the ventral and lateral surfaces of both ventricles at a restricted site between the root of the ascending aorta and the pulmonary trunk. The dorsal surface of both ventricles is supplied by several epicardial nerves extending from the left dorsal ganglionated nerve subplexus on the dorsal left atrium. Ventral accessing nerves are thicker and more numerous than dorsal nerves. Intrinsic ventricular NS are rare on the conus arteriosus and the root of the pulmonary trunk. The number of ventricular NS ranged from 11 to 220 per heart. Four chemical phenotypes of NS within ventricular ganglia were identified, i.e. ganglionic cells positive for choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and biphenotypic, i.e. positive for both ChAT/nNOS and for ChAT/tyrosine hydroxylase. Clusters of small intensely fluorescent cells are distributed within or close to ganglia on the root of the pulmonary trunk, but not on the conus arteriosus. The largest and most numerous intrinsic nerves proceed within the epicardium. Scarce nerves were found near myocardial blood vessels, but the myocardium contained only a scarce meshwork of NFs. In the endocardium, large numbers of thin nerves and NFs proceed along the bundle of His and both its branches up to the apex of the ventricles. The endocardial meshwork of fine NFs was approximately eight times denser than the myocardial meshwork. Adrenergic NFs predominate considerably in all layers of the ventricular walls and septum, whereas NFs of other neurochemical phenotypes were in the minority and their amount differed between the epicardium, myocardium and endocardium. The densities of NFs positive for nNOS and ChAT were similar in the epicardium and endocardium, but NFs positive for nNOS in the myocardium were eight times more abundant than NFs positive for ChAT. Potentially sensory NFs positive for both calcitonin gene-related peptide and substance P were sparse in the myocardial layer, but numerous in epicardial nerves and particularly abundant within the endocardium. Electron microscopic observations demonstrate that intrinsic ventricular nerves have a distinctive morphology, which may be attributed to remodelling of the peripheral nerves after their access into the ventricular wall. In conclusion, the rabbit ventricles display complex structural organization of intrinsic ventricular nerves, NFs and ganglionic cells. The results provide a basic anatomical background for further functional analysis of the intrinsic nervous system in the cardiac ventricles.

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum.

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517-2788; aged) vs. 2118 ± 108 (range 1513-2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans.

Neuroanatomy of the murine cardiac conduction system: a combined stereomicroscopic and fluorescence immunohistochemical study.

The mouse heart is a popular model to study the function and autonomic control of the specialized cardiac conduction system (CCS). However, the precise identity and anatomical distribution of the intrinsic cardiac nerves that modulate the function of the mouse CCS have not been adequately studied. We aimed at determining the organization and distribution of the intrinsic cardiac nerves that supply the CCS of the mouse. In whole mouse heart preparations, intrinsic neural structures were revealed by histochemical staining for acetylcholinesterase (AChE). Adrenergic, cholinergic and peptidergic neural components were identified, respectively, by immunohistochemical labeling for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), calcitonin gene related peptide (CGRP), substance P (SP), and protein gene product 9.5 (PGP 9.5). Myocytes of the CCS were identified by immunolabeling of hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4). In addition, the presence of CCS myocytes in atypical locations was verified using fluorescent immunohistochemistry performed on routine paraffin sections. The results demonstrate that four microscopic epicardial nerves orientated toward the sinuatrial nodal (SAN) region derive from both the dorsal right atrial and right ventral nerve subplexuses. The atrioventricular nodal (AVN) region is typically supplied by a single intrinsic nerve derived from the left dorsal nerve subplexus at the posterior interatrial groove. SAN myocytes positive for HCN4 were widely distributed both on the medial, anterior, lateral and even posterior sides of the root of the right cranial (superior caval) vein. The distribution of HCN4-positive myocytes in the AVN region was also wider than previously considered. HCN4-positive cells and thin slivers of the AVN extended to the roots of the ascending aorta, posteriorly to the orifice of the coronary sinus, and even along both atrioventricular rings. Notwithstanding the fact that cholinergic nerve fibers and axons clearly predominate in the mouse CCS, adrenergic nerve fibers and axons are abundant therein as well. Altogether, these results provide new insight into the anatomical basis of the neural control of the mouse CCS.

Radiofrequency catheter ablation of pulmonary vein roots results in axonal degeneration of distal epicardial nerves.

BACKGROUND: In treatment of atrial fibrillations (AF), radiofrequency ablation (RFA) at the pulmonary vein (PV) roots isolates AF triggers in the myocardial sleeves, but also can destroy PV ganglia and branches of the intrinsic cardiac nerve plexus. AIM: To determine the long-term impact of RFA at the PV roots on the structure of epicardial nerves located distally from the RFA site. METHODS: Five black-faced sheep underwent epicardial RFA of the left and middle PV roots. Two to 3 months after RFA, we obtained samples of epicardial nerves from remote locations of the left dorsal (LD) neural subplexus that extends along the roots of the superior PVs toward the coronary sinus (CS) and dorsal left ventricle (LV). Right atrial epicardial nerves from the right ventral (RV) neural subplexus of the ablated animals and epicardial nerves from LD neural subplexus of five additional intact sheep were used as control. Nerve morphology was examined using histochemical, immunohistochemical and transmission electron microscopy. RESULTS: Histochemical acetylcholinesterase staining did not reveal any epicardial nerve alterations. However, tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) staining showed clearly the reduced numbers of TH and ChAT immunoreactive (IR) nerve fibers within epicardial nerves derived from the remote LD subplexus; control samples from all examined animals were full of evenly distributed TH-IR and ChAT-IR nerve fibers. In sharp contrast to control nerves, numerous swollen or disintegrated axons and Schwann cells with pyknotic nuclei inside unmyelinated and myelinated nerve fibers were identified by electron microscopy of ultrathin sections of epicardial nerves from the CS and LV regions in all ablated animals. CONCLUSIONS: Degeneration of remote atrial and ventricular epicardial nerves is evident 2-3 months after epicardial RFA at the PV roots. Such nerves are likely to be non-functional. Therefore, long-term autonomic dysfunction is a potential risk of PV isolation by RFA.

Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations.

BACKGROUND: The intrinsic neural plexus of the mouse heart has not been adequately investigated despite the extensive use of this species in experimental cardiology. OBJECTIVE: The purpose of this study was to determine the distribution of cholinergic, adrenergic, and sensory neural components in whole-mount mouse heart preparations using double immunohistochemical labeling. METHODS/RESULTS: Intrinsic neurons were concentrated within 19 ± 3 ganglia (n = 20 mice) of varying size, scattered on the medial side of the inferior caval (caudal) vein on the right atrium and close to the pulmonary veins on the left atrium. Of a total of 1,082 ± 160 neurons, most somata (83%) were choline acetyltransferase (ChAT) immunoreactive, whereas 4% were tyrosine hydroxylase (TH) immunoreactive; 14% of ganglionic cells were biphenotypic for ChAT and TH. The most intense ChAT staining was observed in axonal varicosities. ChAT was evident in nerve fibers interconnecting intrinsic ganglia. Both ChAT and TH immunoreactivity were abundant within the nerves accessing the heart. However, epicardial TH-immunoreactive nerve fibers were predominant on the dorsal and ventral left atrium, whereas most ChAT-positive axons proceeded on the heart base toward the large intrinsic ganglia and on the epicardium of the root of the right cranial vein. Substance P-positive and calcitonin gene-related peptide-immunoreactive nerve fibers were abundant on the epicardium and within ganglia adjacent to the heart hilum. Small intensely fluorescent cells were grouped into clusters of 3 to 8 and were dispersed within large ganglia or separately on the atrial and ventricular walls. CONCLUSION: Although some nerves and neuronal bundles of the mouse epicardial plexus are mixed, most express either adrenergic or cholinergic markers. Therefore, selective stimulation and/or ablation of the functionally distinct intrinsic neural pathways should allow the study of specific effects on cardiac function.

Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart.

BACKGROUND: Both normal and genetically modified mice are excellent models for investigating molecular mechanisms of arrhythmogenic cardiac diseases that may be associated with an imbalance between sympathetic and parasympathetic nervous input to the heart. OBJECTIVE: The purpose of this study was to (1) determine the structural organization of the mouse cardiac neural plexus, (2) identify extrinsic neural sources and their relationship with the cardiac plexus, and (3) reveal any anatomic differences in the cardiac plexus between mouse and other species. METHODS: Cardiac nerve structures were visualized using histochemical staining for acetylcholinesterase (AChE) on whole heart and thorax-dissected preparations derived from 25 mice. To confirm the reliability of staining parasympathetic and sympathetic neural components in the mouse heart, we applied a histochemical method for AChE and immunohistochemistry for tyrosine hydroxylase (TH) and/or choline acetyltransferase (ChAT) on whole mounts preparations from six mice. RESULTS: Double immunohistochemical labeling of TH and ChAT on AChE-positive neural elements in mouse whole mounts demonstrated equal staining of nerves and ganglia for AChE that were positive for both TH and ChAT. The extrinsic cardiac nerves access the mouse heart at the right and left cranial veins and interblend within the ganglionated nerve plexus of the heart hilum that is persistently localized on the heart base. Nerves and bundles of nerve fibers extend epicardially from this plexus to atria and ventricles by left dorsal, dorsal right atrial, right ventral, and ventral left atrial routes or subplexuses. The right cranial vein receives extrinsic nerves that mainly originate from the right cervicothoracic ganglion and a branch of the right vagus nerve, whereas the left cranial vein is supplied by extrinsic nerves from the left cervicothoracic ganglion and the left vagus nerve. The majority of intrinsic cardiac ganglia are localized on the heart base at the roots of the pulmonary veins. These ganglia are interlinked by interganglionic nerves into the above mentioned nerve plexus of the heart hilum. In general, the examined hearts contained 19 ± 3 ganglia, giving a cumulative ganglion area of 0.4 ± 0.1 mm(2). CONCLUSION: Despite substantial anatomic differences in ganglion number and distribution, the structural organization of the intrinsic ganglionated plexus in the mouse heart corresponds in general to that of other mammalian species, including human.

Epicardial neural ganglionated plexus of ovine heart: anatomic basis for experimental cardiac electrophysiology and nerve protective cardiac surgery.

BACKGROUND: Sheep are routinely used in experimental cardiac electrophysiology and surgery. OBJECTIVE: The purpose of this study was to (1) ascertain the topography and architecture of the ovine epicardial neural plexus (ENP), (2) determine the relationships of ENP with vagal and sympathetic cardiac nerves and ganglia, and (3) evaluate gross anatomic differences and similarities of ENP in humans, sheep, and other species. METHODS: Ovine ENP and extrinsic sympathetic and vagal nerves were stained histochemically for acetylcholinesterase in whole heart and/or thorax-dissected preparations from 23 newborn lambs, with subsequent examination by stereomicroscope. RESULTS: Intrinsic cardiac nerves extend from the venous part of the ovine heart hilum along the roots of the cranial (superior) caval and left azygos veins to both atria and ventricles via five epicardial routes: dorsal right atrial, middle dorsal, left dorsal, right ventral, and ventral left atrial nerve subplexuses. Intrinsic nerves proceeding from the arterial part of the heart hilum along the roots of the aorta and pulmonary trunk extend exclusively into the ventricles as the right and left coronary subplexuses. The dorsal right atrial, right ventral, and middle dorsal subplexuses receive the main extrinsic neural input from the right cervicothoracic and right thoracic sympathetic T(2) and T(3) ganglia as well as from the right vagal nerve. The left dorsal is supplied by sizeable extrinsic nerves from the left thoracic T(4)-T(6) sympathetic ganglia and the left vagal nerve. Sheep hearts contained an average of 769 +/- 52 epicardial ganglia. Cumulative areas of epicardial ganglia on the root of the cranial vena cava and on the wall of the coronary sinus were the largest of all regions (P <.05). CONCLUSION: Despite substantial interindividual variability in the morphology of ovine ENP, right-sided epicardial neural subplexuses supplying the sinoatrial and atrioventricular nodes are mostly concentrated at a fat pad between the right pulmonary veins and the cranial vena cava. This finding is in sharp contrast with a solely left lateral neural input to the human atrioventricular node, which extends mainly from the left dorsal and middle dorsal subplexuses. The abundance of epicardial ganglia distributed widely along the ovine ventricular nerves over respectable distances below the coronary groove implies a distinctive neural control of the ventricles in human and sheep hearts.

Nerve supply of the human pulmonary veins: an anatomical study.

BACKGROUND: Atrial ectopic discharges originating in the pulmonary veins (PVs) are known to initiate atrial fibrillation (AF), which may be terminated by catheter-based PV isolation. Because a functional relationship exists between cardiac autonomic effects and PVs in arrhythmogenesis, it has been suggested that discharges of the nerves that proceed to the PVs and interconnect with intrinsic ganglionated nerve plexuses are potential triggers of AF in man. OBJECTIVE: This study sought to determine the characteristics and distribution of neural routes by which autonomic nerves supply the human PVs. METHODS: We examined the intrinsic neural structures of 35 intact (nonsectioned) left atrial (LA)-PV complexes stained transmurally for acetylcholinesterase using a stereomicroscope. RESULTS: The epicardial ganglionated nerves pass onto the extrapulmonary segments of the human PVs from the middle, left dorsal, and dorsal right atrial subplexuses. The left and right inferior PVs involved a lesser number of ganglia than the left and right superior PVs. Abundant extensions of epicardial nerves penetrate transmurally the PV walls and form a patchy neural network beneath the endothelium of PVs. The subendothelial neural meshwork with numerous free nerve endings, which appeared to be typical sensory compact nerve endings, was mostly situated at the roots of the 4 PVs. No ganglia were identified beneath the endothelium of the human PVs. CONCLUSION: The richest areas containing epicardial ganglia, from which intrinsic nerves extend to the human PVs, are concentrated at the inferior surface of both the inferior and left superior PVs. Therefore, these locations might be considered as potential targets for focal pulmonary vein ablation in catheter-based therapy of AF.

Innervation of pulmonary veins: morphologic pattern and pathways of nerves in the human fetus.

The aim of the study was to determine the anatomy of intrinsic nerves supplying human pulmonary veins (PVs). Twenty-two hearts of human fetuses with full sets of PVs were examined using a histochemical method for acetylcholinesterase in order to stain transmurally intrinsic neural structures on non-sectioned PVs for subsequent stereomicroscopic examination. Findings of the study demonstrate that epicardiac nerve extensions from both the dorsal right atrial and the middle dorsal subplexuses reached the right superior as well as the right inferior PVs, whereas the left superior PV was supplied by nerve extensions from the left dorsal subplexus. The left and middle dorsal subplexuses contributed nerves to the left inferior PV. The ganglia related topographically to PVs were patchy in distribution. On the left and right superior PVs, 38+/-6 and 31+/-3 ganglia were found, respectively, whereas 46+/-7 and 38+/-7 ganglia were identified on the left and right inferior PVs. The size of ganglia was similar for all four veins, ranging in area from 0.004+/-0.0003 to 0.007+/-0.0004 mm(2). The total area of ganglia distributed on a given PV was similar, ranging from 0.15+/-0.0003 to 0.25+/-0.0004 mm(2). The present findings demonstrate that the richest ganglion sites supplying intrinsic nerves to the human PVs are located on the posterior sides of both inferior and the left superior PVs and, therefore, these sites may be considered primary targets for focal pulmonary vein ablation in catheter-based therapy of atrial fibrillation.

Location and variability of epicardiac ganglia in human fetuses.

The aim of the study was to determine the morphology of epicardiac ganglia in human fetuses at different stages of their development as these ganglia are considered to be of a pivotal clinical importance. Twenty-one fetal hearts were investigated applying a technique of histochemistry for acetylcholinesterase to visualize the epicardiac neural ganglionated plexus with its subsequent stereoscopic examination on total organs. In all of the examined fetuses, epicardiac neural plexus with numerous ganglia was well recognizable and could be clearly differentiated into seven ganglionated subplexuses, topography and structural organization of which were typical for hearts of adult human. The largest ganglion number comprising 77% of all counted ganglia was identified on the dorsal atrial surface. Fetal epicardiac plexus in gestation period of 15-40 weeks contained 929 +/- 62 ganglia, but ganglion amount did vary substantially from heart to heart. In conclusion, this study implies that the human fetal epicardiac ganglia occupy their definitive location already at gestation period from 15 weeks and their number as well as distribution on heart surface presumably is not age dependent.

[Distribution of the epicardiac neural ganglia in human fetuses of different age]. / Epikardiniu nerviniu mazgu pasiskirstymas skirtingo amziaus zmogaus vaisiuje.

OBJECTIVE: The epicardiac neural ganglia of the adult human heart are distributed in the seven neural ganglionated subplexuses. The aim of the present investigation was to determine the distribution of the epicardiac ganglia in human fetuses of different age, because intrinsic cardiac nervous system of the human fetus has not been enough investigated so far. MATERIAL AND METHODS: In the present study seventeen human fetus hearts were investigated, in which epicardiac neural ganglionated plexus was visualized by histochemical method for acetylcholinesterase. RESULTS: Analysis of the total hearts preparations showed that: (1) the epicardiac neural ganglionated plexus of the fetus at fifteen weeks of gestation has already differentiated into seven ganglionated subplexuses, structure of which is typical for the adult human heart; (2) the epicardiac plexus of fetuses at 15-40 weeks of gestation contains on average 865+/-40 epicardiac ganglia, that may widely range in number from 644 to 1193; (3) the largest number of the neural ganglia is concentrated on the posterior surface of both atria, where up to 76% of all ganglia maybe located; (4) the difference between the number of epicardiac ganglia in the human fetuses at the early (15-25 weeks) and late (26-40 weeks) stages of fetogenesis is not statistically significant (p>0.05). In conclusion, both the distribution and the number of the epicardiac ganglia of fetuses ranging from 15 to 40 weeks of gestation are not age-dependent but varied substantially from heart to heart.