Quantitative study of nerves of the human left atrium

2004

Summary Objectives: of the present study were to verify the topography of the intracardiac nerve subplexuses (INS) by using electrophysiological methods, its relations with sinoatrial (SA) node function and investigate the possibility of selective surgical SA node denervation. Design, Methods and Results: 32 mongrel dogs were used for electrophysiological studies. Nervus subplexuses destructions were performed by electrocoagulation or cryoablation in three zones located around the right superior vena cava: ventral, lateral and dorsal. The sinus rhythm, SA node function recovery time, atrioventricular (AV) node conductivity, the AV node and the atrial effective refractory period were measured. Eight experiments in each of the three zones were performed. The average changes of electrophysiological parameters before and after INS destruction have shown that the destruction of the ventral and lateral zones modifies the effects of sympathetic tone to SA node activity. The destruction of ...

Heart Rhythm, 2011

BACKGROUND Atrial fibrillation (AF) is a multifactorial disease of the atria. OBJECTIVE We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR). METHODS Preparation of postmortem isolated hearts of subjects with documented persistent AF (group A) and SR (group B) included: (1) histological sectioning of predefined areas and quantification of nerve density, and (2) differentiation using immunohistochemistry in adrenergic (sympathetic, tyrosine-hydroxylase antibody), cholinergic (parasympathetic, choline-acetyltransferase antibody) and mixed (adrenergic and cholinergic staining) nerves. RESULTS Characteristics of subjects in group A (N ϭ 15) and group B (N ϭ 24) did not differ. The mean overall nerve density was similar between groups (A: 0.31 Ϯ 0.25/mm 2 ; B: 0.35 Ϯ 0.25/mm 2 ; P ϭ .87). Nerve density appeared higher in the region of the pulmonary vein ostia and antrum (group A: 0.38 Ϯ 0.21/ mm 2 ; group B: 0.32 Ϯ 0.19/mm 2 ,) compared with other locations of the right and left atrium. A total of 2,224 (group A: 685; group B: 1539) nerves were differentiated using immunohistochemistry. There was a high degree of colocalization of adrenergic and cholinergic nerves (group A: 80% mixed staining, group B: 69% mixed staining). In group A hearts there was a significantly lower density of predominantly cholinergic nerves (0.025 Ϯ 0.052/mm 2 vs. 0.058 Ϯ 0.099/mm 2 ; P ϭ .008) and a higher density of nerves containing adrenergic components (0.24 Ϯ 0.18/mm 2 vs. 0.18 Ϯ 0.17/mm 2 , P ϭ .046). CONCLUSION Overall autonomic nerve density did not differ between atria with persistent AF compared with SR. On a morphological level, we detected a shift toward a lower density of cholinergic nerves and a higher density of nerves containing adrenergic components in AF subjects. KEYWORDS Atrial fibrillation; Autonomic nervous system; Histopathology ABBREVIATIONS ANS ϭ autonomic nervous system; AF ϭ atrial fibrillation; ChAT ϭ choline acetyltransferase; ECG ϭ electrocardiogram; PV ϭ pulmonary vein; SR ϭ sinus rhythm; TH ϭ tyrosine hydroxylase

Journal of Electrocardiology, 2007

Objectives: of the present study were to verify the topography of the intracardiac nerve subplexuses (INS) by using electrophysiological methods, its relations with sinoatrial (SA) node function and investigate the possibility of selective surgical SA node denervation. Design, Methods and Results: 32 mongrel dogs were used for electrophysiological studies. Nervus subplexuses destructions were performed by electrocoagulation or cryoablation in three zones located around the right superior vena cava: ventral, lateral and dorsal. The sinus rhythm, SA node function recovery time, atrioventricular (AV) node conductivity, the AV node and the atrial effective refractory period were measured. Eight experiments in each of the three zones were performed. The average changes of electrophysiological parameters before and after INS destruction have shown that the destruction of the ventral and lateral zones modifies the effects of sympathetic tone to SA node activity. The destruction of the dorsal zone modifies the effects of the vagus nerve to the SA node. Conclusions: The function of the SA and AV nodes can be modified by the destruction of the ventral, lateral and dorsal zones of the right atrium. It is necessary to point up that while performing interventions and radiofrequency ablations in the zones of nerve plexuses surgeons must be aware of possible changes in SA node's function because of the impairment of these nerve plexuses and, if possible, to avoid surgical manipulations in these zones.

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.

2017

Journal of Nuclear Cardiology, 2019

Initiation of the cardiac cycle is myogenic, originating in the sinuatrial node (SA). It is harmonizied in rate, force and output by autonomic nerves which operate on the nodal tissues and their prolongations, on coronary vessels and on the working atrial and ventricular musculature. All the cardiac branches of the N.vagus, X. cranial nerve, (parasympathetic) and all the sympathetic branches (except the cardiac branch of the superior cervical sympathetic ganglion) contain both afferent and efferent fibres; the cardiac branch of the superior cervical sympathetic ganglion is entirely efferent. Sympathetic fibres accelerate the heart and dilate the coronary arteries when stimulated, whereas parasympathetic (vagal) fibres slow the heart and cause constriction of coronary arteries. Preganglionic cardiac SY (sympathetic) axons arise from neurones in the intermediolateral column of the upper four or five thoratic spinal segments. Some synapse in the corresponding upper thoratic SY ganglia, others ascend to synapse in the cervical ganglia; postganglionic fibres from these ganglia form the SY cardiac nerves (from ganglion cervicale sup. goes N.cardiacus cervicalis sup.; form ganglion cervicale med. Goes N.cardiacus cervicalis sup.; from ganglion cervicothoracicum(stellatum) goes N.cardiacus cervicalis inf.; from ganglion thoracicum I-IV go Nn.cardiaci thoracici). Preganglionaric cardiac PSY (parasympathetic) axons arise from neurones in either the dorsal vagal nucleus ambiguus; they run in vagal cardiac branches to synapse in the cardiac plexuses and atrial walls. In man (like in most mammals) intrinsic cardiac neurones are limited to the atria and interatrial septum, and are most numerous in the subepicarial connective tissue near the SA and AV nodes.

Journal of Interventional Cardiac Electrophysiology, 2006

In mammalian ventricles including humans, it is recognized that parasympathetic ganglia innervate the heart. Little is known about the location and function of right ventricular parasympathetic nerves in humans. We hypothesized that in humans: (1) there are parasympathetic ganglia that supply the right ventricle that can be stimulated via an endocardial catheter and (2) stimulation of these fibers will alter the electrical and hemodynamic function of the right ventricle. Parasympathetic nerve stimulation was performed via an endocardial catheter placed along several sites of the right ventricle, superior vena cava, and right internal jugular area in humans. The spatial extent of parasympathetic innervation was mapped in 1-cm zones across the right ventricle. Cardiac output, heart rate, and atrioventricular conduction were monitored to provide independent assessment of parasympathetic innervation. In all 22 patients, ventricular refractoriness shortened from 12 ± 3 to 3 ± 1 ms during parasympathetic nerve stimulation, and the greatest shortening of refractoriness was observed at the base of the right ventricle ( p = 0.01). No significant shortening in ventricular refractoriness occurred in areas beyond 2 cm from the right ventricular base. These results were compared by using T table test. The parasympathetic nerve stimulation protocol decreased cardiac output, reaffirming the principle effect of parasympathetic ganglia. Atropine was administered in seven patients. All effects from nerve stimulation were abolished after atropine administration. These results were also compared by using T table test.

On reaching the heart, extrinsic cardiac nerves relay their signal to a network of autonomic ganglia situated throughout the epicardial surface. These ganglia interconnect and form a complex intrinsic ganglionated neural plexus responsible for integrating central and local inputs and relaying this signal to the cardiac conduction system, coronary vessels, heart valves and contractile muscle fibres. Within the human heart this intracardiac plexus could be defined in terms of seven subplexuses located and innervating discrete areas of the heart. Despite some noticeable адам мен interspecific differences in the overall neuronal number and ganglionic morphology, this type of structural organization is conserved throughout the mammalian heart. Intrinsic ganglionated plexus consists of neurons expressing various modulatory agents. It is widely accepted that most intracardiac neuronal somata are cholinergic, yet nearly half of them are biphenotypic for either tyrosine hydroxylase or neuronal nitric oxide synthase. Moreover exclusively tyrosine hydroxylase positive somata are found in some mammals and human hearts. Therefore in addition to relaying preganglionic vagal impulses, cardiac ganglia also integrate sensory and sympathetic inputs for rapid temporal reflexes and local regulation of heart rate on a beat-to-beat basis. The epicardium, in addition to numerous ganglia, is the main milieu for distribution of nerves towards the heart apex. The myocardium contains both scarce nerves located in the vicinity of blood vessels and a meshwork of fine nerve fibers. The endocardium contains a dense network of nerve fibers and nerve bundles with only a small part of them coalescing into nerves. The described structural organization of intracardiac nervous system provides an anatomical basis of the autonomic control of circulation.

2009

The heart is an organ which main characteristic is its autonomy of function. Therefore, it is possible to develop elementary experiments such as extirpating the heart of a frog (Bufo amenarum), which during a certain amount of time keeps beating and even responding to brady-or tachycardian chemical stimulations. The underlying cause of this phenomenon is the action of specific solutions, which shower the mentioned organ. However, inside the organism, it adapts its functions to the somatic reality and to the specific moment of that soma. These conducts are instrumented by a complex system of information gathering, the adoption of central nervous system's function standards, and the production of functional responses suitable for the different possible situations. All these functions are related to cardiac innervation. © Neuroanatomy. 2009; 8: 26-31.