Electrophysiological effects of the antiarrhythmic agent GYKI-23107 in dogs

Cardiac electrophysiological properties of GYKI-23107, a new membrane stabilizing antiarrhythmic agent were studied in anaesthetized open-chest dogs. Epi- end endocardial electrograms (for sinus potential and for His bundle recording) were obtained during sinus rhythm and following atrial and ventricular pacing. The registration were performed under control conditions as well as five minutes after drug administration of 8 mg/kg slow i.v. or 20 minutes after 20 mg/kg intraduodenal administration respectively. GYKI-23107 did not influence significantly either the sinus cycles, PA-intervals, sinus node potentials, or the classical electrophysiological parameters of sinoatrial function as the corrected recovery time of the sinus node, sino-atrial conduction time or the secondary post-stimulation sinus cycles before and after vegetative blockade. Neither the AH intervals, anterograde Wenckebach period, nor ventriculo-atrial conduction time changed significantly. QRS duration, configuration and HV-intervals remained also unchanged after drug administration in doses which used in this study, and which seemed to be in therapeutic range. The agent did not influence significantly the effective refractory periods of the atrium and ventricle during sinus rhythm. This study suggest that the GYKI-23107 is not depressive on the anterograde (AV), retrograde (VA), intraventricular conduction and is slightly depressive on the intrinsic pacemaker properties.     

Electrophysiological features in patients with sinus node dysfunction and vasovagal syncope

Introduction

Syncope is a common presentation of sinus node dysfunction (SND). Some patients who receive a permanent pacemaker due to SND do not benefit from it and further diagnostic workup leads to the diagnosis of vasovagal syncope (VVS). The aim of the study was to identify electrophysiological criteria that can be used for identification of patients with SND and concurrent VVS.

Material and methods

Transoesophageal atrial pacing (TAP) was performed in 100 patients divided into four groups depending on symptoms and TAP results. Standard electrophysiological parameters of sinus node function and their variability were obtained in the basal state and after pharmacological autonomic blockade (AB).

Results

Patients with concurrent SND and VVS had a greater variability of sinoatrial conduction time assessed by Strauss’ method than patients without incidents of syncope (83.2 ±53.9 vs. 34.1 ±19.6, 47.8 ±33.6 and 32.1 ±22.99). Apart from abnormal sinus node recovery time and second pause, patients with SND had bigger basal state variability of these parameters. In patients with SND and concurrent vasovagal syncope the variability of sinus node recovery time (SNRT), corrected SNRT (cSNRT) and second pause (IIP) decreased after autonomic blockade.

Conclusions

Patients with concurrent SND and VVS have distinct electrophysiological features – greater sinoatrial conduction time (SACT) variability and the decrease of SNRT, cSNRT and IIP variability after AB. However, further studies in larger study groups are needed to validate our findings. Transoesophageal atrial pacing is a useful procedure in patients with syncope, especially when the coexistence of more than one cardiac cause is suspected.     

Pathophysiological characteristics, diagnostic problems and assessment of sinus node dysfunction

Based on clinical and experimental experience, sick sinus syndrome can be divided into two groups: intrinsic and autonomic neurovegetative pacemaker dysfunction. Sinus node activity is characterized electrophysiologically by automaticity, recovery and sinoatrial conduction. The automaticity of the sinus pacemaker cell groups and sinus recovery can be differentiated properly under experimental conditions. Studies of the electrophysiological characteristics showed the basic functional parameters to be normal in autonomic sinus dysfunction. Diagnosis is either based on clinical observation or on the data of Holter monitoring, the electrophysiological methods being inadequate for diagnosing this neurovegetative form of sick sinus syndrome. On the other hand, intrinsic-organic sinus dysfunction can be diagnosed by electrophysiological tests. If completed by complex pharmacological studies, in this organic form of sick sinus syndrome, even the severity of the intrinsic injuries can be assessed quantitatively. This division provides a logical basis for a proper selection and evaluation of the differential diagnostic procedures, while information on the aetiopathology of sinus dysfunction and on the degree of the functional injuries of the electrophysiological structure of the heart provides an adequate basis for therapy.     

Developmental anatomy of HNK-1 immunoreactivity in the embryonic rat heart: co-distribution with early conduction tissue

To investigate the origin and development of the cardiac conduction system, the distribution of HNK-1 immunoreactivity in embryonic rat hearts was studied in histological sections and in three-dimensional computer reconstructions. Earliest HNK-1 reactivity was found along the endocardial surface of the fusing tubular heart at 9.5 embryonic days (ED) and subsequently within individual myocytes scattered widely along the looped tubular heart. Immunopositive myocytes appeared along the earliest ventricular trabeculae as they coalesced to form the developing interventricular septum during day 11, spreading to either side to give rise to the right and left bundle branches in the 12.5 ED heart. In the venous pole of the heart, primordia of the sinus node, and of the transient left sinus node, appeared immunopositive from 12.5 ED, coalescing during ED 13 along the anterior wall of the right sinus horn or developing coronary sinus, respectively. In the atria, several distinct tracts of immunoreactive myocytes were defined by 14.5 ED, ramifying from the sinoatrial junction to the atrial appendages or to the atrio-ventricular (AV) junction near the AV node. The timing and distribution of these immunostaining patterns suggest that ventricular conduction tissue develops within the earliest trabecular and septal myocardium, and is distinct from later immunopositive atrial tracts and extracardiac cell populations, such as neural crest, that appear to contribute to formation of the sinus node and autonomic innervation of the heart.     

Pathological Aspects of Radiofrequency Catheter Ablation of the Canine Atrioventricular Node and Bundle of His

Radiofrequency catheter ablation of the atrioventricular (AV) node or bundle of His was performed in 12 adult mongrel dogs. The aim was to create chronic incomplete AV block (first- and second-degree AV block) and to examine the histopathology of the ablated lesions. However, the late electrophysiological results (2 4 weeks follow up) were various: normal in 2 dogs, mild PR prolongation (< 50%) in 2 dogs, first-degree AV block (PR prolongation a 50%) in 2 dogs, second degree AV block in 2 dogs, complete AV block in 4 dogs. The maximally ablated area (%) of the atrioventricular conduction system in serial histologic sections from dogs with these conditions was 69%, 75%, 89.5%, 95% and 99.5%, respectively. The number of intact conduction cells at the maximally ablated site varied from 6 to 30 in the four cases of incomplete AV block. The mean ablated volume (%) of either the AV node or penetrating His bundle correlated roughly with the degree of AV block. The ablated lesions were well demarcated and almost replaced by dense fibrous tissue at 4 weeks. Interruption (3 dogs) or thinning (1 dog) of the endocardial elastic lamellae was detected, in association with endocardial thickening (mean 913 μm). Endocardial thrombi were found in 3 dogs (2 fresh, 1 organized). We conclude that radiofrequency catheter ablation does not cause severe complicated lesions. Several possible conditions for creating chronic incomplete AV block are discussed. Acta Pathol Jpn 41: 487–498, 1991.     

Anatomy of the sinus node,av node,and his bundle of the heart of the sperm whale (Physeter macrocephalus), with a note on the absence of an os cordis

Background: Atrioventricular (AV) conduction time in large whales is only slightly greater than in smaller mammals even though their hearts are enormously larger. Little is known of the detailed histology or cytology of the conduction system of large whales. Such knowledge could be useful in defining the nature of cardiac rhythm and conduction of the whale as well as smaller mammals including humans. Methods: We studied hearts from seven sperm whales. After fixation in formaldehyde and later dissection, specimens were prepared for histological examination. Results: Cell size, histological organization, and innervation of the sperm whale's sinus node, AV node, and His bundle are similar to most mammalian hearts, except the sinus node is substantially larger. There is no central fibrous body between the atrial and ventricular septa, and the whale has no os cordis. Only the upper quarter of the interventricular septum is fully formed; below that there is only a thin layer of fatty connective tissue between the two ventricles. Conclusions: Given our morphological findings, we believe that the whale's comparatively short AV conduction time may be best explained by the sinus node and AV node functioning as coupled relaxation oscillators. Absence of an os cordis or central fibrous body or strong attachment between the two ventricles may pose both electrophysiological and hemodynamic hazards when the whale is no longer in its normally buoyant aquatic environment. © 1995 Wiley-Liss, Inc.     

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 μM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.     

Incidence of rhythm disorders in hyperthyrosis with special respect of old age form

Sinus tachycardia and atrial fibrillation are frequent features in hyperthyrosis while sinus node dysfunction is regarded as a rare complication. Bradycardia may cause diagnostic problems mainly in atypical hyperthyrosis of the old age. The authors analysed distribution and age related association of the rhythm disorders in hyperthyrosis. In case of the appearance of Sick Sinus Syndrome (SSS), parameters representing the function of sinus node were studied by electrophysiological investigations. Above the age of 50 years incidences of atrial fibrillation and SSS were significantly increased. The abnormal sinus node function proved to be reversible in a portion of the cases. In old age, in case of occurrence of the symptoms of SSS, possibility of hyperthyrosis also should be considered, especially when indication of permanent pacemaker is established.     

Cardiac conduction system in the chicken: Gross anatomy plus light and electron microscopy

Twenty-three chicken hearts were used to study the cardiac conduction system by light and electron microscopy. In addition to a sinus node, atrioventricular node (AVN), His bundle, left and right bundle branches (LBB, RBB), the chicken also has an AV Purkinje ring and a special middle bundle branch (MBB). The sinus node lies near the base of the lower portion of the right sinoatrial valve. The AV node is just above the tricuspid valve and anterior to the coronary sinus. The His bundle descends from the anterior and inferior margin of the AV node into the interventricular septum, then dividing into right, left and middle branches some distance below the septal crest. The middle bundle branch turns posteriorly toward the root of the aorta. The AV Purkinje ring originates from the proximal AV node and then encircles the right AV orifice, joining the MBB to form a figure-of-eight loop. The chicken conduction system contains four types of myocytes: (1) The P cell is small and rounded, with a relatively large nucleus and sparse myofibrils. (2) The transitional cell is slender and full of myofibrils. (3) The Purkinje-like cell resembles the typical Purkinje cell, but is smaller and darker. (4) The Purkinje cell is found in the His bundle, its branches, and the periarterial and subendocardial Purkinje network. © 1993 Wiley-Liss, Inc.     

A method of study of the pathology of the conduction system for electrocardiographic and his bundle electrogram correlations

There have been advances in electrophysiology which have necessitated a more thorough semi-quantitative analysis of the entire conduction system to yield data useful for correlation purposes. Thus an attempt is made to modify and expand our previous method of studying the conduction system pathologically. This method thus includes the study of the sinoatrial (SA) node and its approaches, the atrial preferential pathways, the approaches to the atrioventricular (AV) node, the AV node, the penetrating and branching portions of the AV bundle, the bundle branches, the peripheral Purkinje nets, and the remainder of the atrial and ventricular myocardium. The SA node and its approaches are studied in a longitudinal manner. This gives a better insight into the pathologic changes than does a study in the transverse direction. The approaches to the AV node, bundle and bundle branches are studied in an oblique manner, rather than horizontally apicalward, or from the posterior to the anterior septal region. The horizontal manner does not give sufficient sampling of the AV node and bundle unless complete serial sections are made. Sectioning from the posterior to the anterior septal wall makes difficult an evaluation of the right bundle branch. In conduction system correlation with Wolff-Parkinson-White and Lown-Ganong-Levine syndromes complete serial sectioning of both AV rims is advisable. Where complete serial sectioning is impossible in large adult hearts, retaining every fifth section may be permissable. In the study of congenitally abnormal hearts, it is advisable to embed the entire heart as a unit. If that is impossible because of the size of the heart, then very careful judicious planning of the fashioning of the blocks is necessary, so that displaced SA nodes, and anterior AV nodes and bundles are not overlooked.     

HISTOPATHOLOGICAL STUDY OF THE CONDUCTION SYSTEM OF THE HEART IN DUCHENNE PROGRESSIVE MUSCULAR DYSTROPHY

The cardiac conduction systems including sinoatrial (SA) node, atrioventricular (AV) node, atrioventricular(His) bundle, and peripheral conduction system (left and right bundle branch, and Purkinje fiber) of 23 patients with Duchenne progressive musculr dystrophy(DMD) were studied with light microscope. Infiltration of fat tissue and mild fibrosis were occasional findings in SA and AV nodes. Degeneration of the conduction muscle fiber was hardly noted in SA node, AV node, and His bundle. Only the peripheral conduction system (Purkinje fiber) showed significant degenerations such as eosinophilic, necrotic and vacuolar changes with fibrosis. These necrobiotic changes resembled hyaline and vacuolar skeletal and cardiac muscular degenerations in DMD and were assumed to have occurred on the basis of the structural and constitutional characteristics of the peripheral conduction fiber as a striated muscle fiber. The vascular changes and amyloid deposit suggesting precocious aging in the conduction systems were not observed.     

The secondary poststimulative phase after rapid atrial pacing: its importance in the diagnosis of sinus node dysfunction

The effect of atropine and the beta-blocker Tobanum was studied on intrinsic heart rate (IHR) and on rapid atrial pacing carried out before and after administration of the drugs. The primary and secondary postpacing parameters were examined in both circumstances. In patients with normal IHR, return to the basic heart frequency after the drugs showed an exponential characteristic while in patients with abnormal IHR, the cycles of PPC 2-10 have lost this characteristic feature. The latter was a more characteristic electrophysiological sign of sinus node dysfunction than the recovery time of the sinus node. In patients with abnormal IHR, maximum CPPC1 is sometimes normal.     

Intravenous magnesium for cardiac arrhythmias: jack of all trades.

Intravenous magnesium has been used to prevent and treat many different types of cardiac arrhythmia. It has diverse electrophysiological actions on the conduction system of the heart; including prolonging sinus node recovery time, and reducing automaticity, atrioventricular nodal conduction, antegrade and retrograde conduction over an accessory pathway, and His-ventricular conduction. Intravenous magnesium can also homogenise transmural ventricular repolarisation. Because of its unique and diverse electrophysiological actions, intravenous magnesium has been reported to be useful in preventing atrial fibrillation and ventricular arrhythmias after cardiac and thoracic surgery; in reducing the ventricular response in acute onset atrial fibrillation, including for patients with Wolff-Parkinson-White syndrome; in the treatment of digoxin induced supraventricular and ventricular arrhythmias, multifocal atrial tachycardia, and polymorphic ventricular tachycardia or ventricular fibrillation from drug overdoses. Intravenous magnesium is, however, not useful in monomorphic ventricular tachycardia and shock-resistant ventricular fibrillation. Large randomised controlled studies are needed to confirm whether intravenous magnesium can improve patient centre outcomes in different cardiac arrhythmias.     

Pathological aspects of radiofrequency catheter ablation of the canine atrioventricular node and bundle of His. With special reference to chronic incomplete atrioventricular block.

Radiofrequency catheter ablation of the atrioventricular (AV) node or bundle of His was performed in 12 adult mongrel dogs. The aim was to create chronic incomplete AV block (first- and second-degree AV block) and to examine the histopathology of the ablated lesions. However, the late electrophysiological results (2-4 weeks follow-up) were various: normal in 2 dogs, mild PR prolongation (less than 50%) in 2 dogs, first-degree AV block (PR prolongation greater than or equal to 50%) in 2 dogs, second-degree AV block in 2 dogs, complete AV block in 4 dogs. The maximally ablated area (%) of the atrioventricular conduction system in serial histologic sections from dogs with these conditions was 69%, 75%, 89.5%, 95% and 99.5%, respectively. The number of intact conduction cells at the maximally ablated site varied from 6 to 30 in the four cases of incomplete AV block. The mean ablated volume (%) of either the AV node or penetrating His bundle correlated roughly with the degree of AV block. The ablated lesions were well demarcated and almost replaced by dense fibrous tissue at 4 weeks. Interruption (3 dogs) or thinning (1 dog) of the endocardial elastic lamellae was detected, in association with endocardial thickening (mean 913 microns). Endocardial thrombi were found in 3 dogs (2 fresh, 1 organized). We conclude that radiofrequency catheter ablation does not cause severe complicated lesions. Several possible conditions for creating chronic incomplete AV block are discussed.     

Disruption of RHOA-ROCK Signaling Results in Atrioventricular Block and Disturbed Development of the Putative Atrioventricular Node

The RHOA-ROCK signaling pathway is involved in numerous developmental processes, including cell proliferation, differentiation and migration. RHOA is expressed in the atrioventricular node (AVN) and altered expression of RHOA results in atrioventricular (AV) conduction disorders in mice. The current study aims to detect functional AVN disorders after disturbing RHOA-ROCK signaling in chicken embryos. RHOA-ROCK signaling was inhibited chemically by using the Rho-kinase inhibitor compound Y-27632 in avian embryos (20 experimental and 29 control embryos). Morphological examination of control embryos show a myocardial sinus venosus to atrioventricular canal continuity, contributing to the transitional zone of the AVN. ROCK inhibited embryos revealed lateralization and diminished myocardial sinus venosus to atrioventricular canal continuity and at the severe end of the phenotype hypoplasia of the AVN region. Ex ovo micro-electrode recordings showed an AV conduction delay in all treated embryos as well as cases with first, second (Wenkebach and Mobitz type) and third-degree AV block which could be explained by the spectrum of severity of the morphological phenotype. Laser capture microdissection and subsequent qPCR of tissue collected from this region revealed disturbed expression of HCN1, ISL1, and SHOX2. We conclude that RHOA-ROCK signaling is essential for normal morphological development of the myocardial continuity between the sinus venosus and AVN, contributing to the transitional zone, and possibly the compact AVN region. Disturbing the RHOA-ROCK signaling pathway results in AV conduction disturbances including AV block. The RHOA-ROCK inhibition model can be used to further study the pathophysiology and therapeutic strategies for AV block. Anat Rec, 302:83–92, 2019. © 2018 Wiley Periodicals, Inc.     

Complete atrioventricular block associated with lymphocytic myocarditis of the atrioventricular node in two young adult dogs

A histological investigation of the atrioventricular (AV) conduction system was performed in two young adult dogs with complete AV block. In both cases, infiltration of lymphocytes and plasma cells into the AV node and loss and disappearance of the conduction fibres were observed. Such inflammatory lesions of the AV conduction system were associated with complete AV block. The aetiology of these changes and the cause of its location at the AV node were not elucidated.     

The AV junction region of the heart: A comprehensive study correlating gross anatomy and direct three‐dimensional analysis. Part I. Architecture and topography

There is little detailed knowledge of the architecture of the AV junction region, the cytoarchitecture of the AV node or of its atrial connections. In the present study, the gross anatomy and topography of intracardiac structures in 21 adult canine hearts were photographically compared in whole and dissected hearts and tissue blocks and serial histologic sections made in three orthogonal planes. There are seven major new findings: 1) A coronary sinus fossa exists at the crux of the heart. It separates the right medial atrial wall (MAW) superoposterior region from the left atrium, its floor is the coronary sinus, and it carries the medial atrionodal bundle and proximal AV bundle on its right wall. 2) The posterior MAW forms two isolated bridges of myocardium as it surrounds the coronary sinus ostium, is isolated from the sinus venarum with crista terminalis and interatrial septum—by the floor of the inferior vena cava, and the narrow bridges link the posterior atrial wall to the mid MAW. 3) The tendon of Todaro has both epicardial and endocardial exposures, terminates in the superoposterior MAW and its medial aspect is adjacent sequentially to the medial atrionodal bundle and proximal AV bundle. 4) Only ordinary myocardium contacts the anulus fibrosus. 5) The ventricular septum's shoulder is humped shape posteriorly, is completely overlaid by anular myocardium and the medial leaflet and is joined by struts of papillary muscle. 6) The membranous septum joins the anterior ventricular septum to the crista supraventricularis, forms part of the posterior noncoronary and right aortic valve sinus walls and encases the right bundle branch. 7) The specialized conduction tissues, the superior, medial and lateral atrionodal bundles, the proximal AV bundle, AV node, distal AV bundle and right bundle branch are subjacent to MAW epicardium outside the right atrium, share regular intracardiac relationships with topographic landmarks and the medial atrionodal bundle, terminal superior atrionodal bundle, the proximal AV bundle and AV node are aligned to the medial leg of Koch's triangle. Thus, atrial myocardium of the AV junction region is that of the MAW. The floor of the inferior vena cava forms a natural barrier to impulse transmission along the full extent of the posterior MAW. The specialized tissues are outside of the MAW. Anatomic landmarks form reliable topographic landmarks for the specialized AV junction region tissues. A knowledge of the association of the specialized conduction tissues with specific regions of the MAW is useful in localizing the tissues and along with the coronary sinus fossa provides several extracardiac approaches. Anat Rec 256:49–63, 1999. © 1999 Wiley‐Liss, Inc.     

The conduction system in human cardiac allografts. A histological and immunopathological study.

Twenty-five hearts were lost in the first 103 orthotopic human cardiac allografts in 100 recipients. Twenty-two patients died. The first nine recipients were treated with Cyclosporin A and high dose Prednisolone and the subsequent recipients were immunosuppressed with a triple regimen consisting of Azathioprine in addition to Cyclosporin A and low dose Prednisolone. Twenty grafts were examined at autopsy and three after retransplantation. Fourteen hearts with acute rejection and vascular pathology were investigated regarding the histological and immunopathological alterations due to cellular and vascular rejection. The recipient sinoatrial node was available for examination in 10, the donor node in 13 and the atrioventricular conductive tissue in all 14 grafts. The conduction system was involved in 8 out of 11 allografts attacked by acute cellular rejection. In one allograft in which the patient developed AV block, the cellular infiltrates were almost exclusively observed in the atrioventricular tissue. Most of the cells were T lymphocytes, while macrophages and B cells were present to a lesser extent. There was little evidence of permanent structural damage to the atrioventricular tissue after recurrent mild or moderate episodes of acute cellular rejection. In the sinus nodes, however, risk of traumatic damage to the recipient and donor sinus node was about half and a quarter respectively. Acute and chronic vascular rejection seemed to be equally distributed in the sinus node, atrioventricular arteries and in the intramural branches of the coronaries. No morphological differences were established between the two types of immunosuppressive regimes.     

The auricular rhythm in patients with the Morgagni-Adams-Stokes syndrome before and after electrical cardiac stimulation

Summary Observations were made on 17 patients with complete or incomplete atrioventricular block complicated by attacks of the Morgagni-Adams-Stokes syndrome. In ten cases the attacks were recorded electrocardiographically. In two patients an enhanced rate of auricular contraction was observed to occur before the attack. During the attacks, in which ventricular asystole lasting for 25 sec or more occurred, the auricular contraction rate was at first increased, and then decreased and arrhythmic. The Erlanger-Blackman phenomenon was found in six patients in which the automatism was initiated in the atrioventricular node.When the rate of electrical stimulation of the ventricles was increased to above the spontaneous rhythm the frequency of the auricular contractions was reduced. In our opinion these changes are reflex. The fact we have described, that a change of sinus autornatism may be induced by electrical stimulation of the ventricles, may help in the choice of the optimal stimulus rhythm.(Presented by Academician A. N. Bakulev) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 4, pp. 19–21, April, 1963     

Morphology and electrophysiology of the mammalian atrioventricular node

The AV node of those mammalian species in which it has been thoroughly investigated (rabbit, ferret, and humans) consists of various cell types: transitional cells, midnodal (or typical nodal cells), lower nodal cells, and cells of the AV bundle. There are at least two inputs to the AV node, a posterior one via the crista terminalis and an anterior one via the interatrial septum, where atrial fibers gradually merge with transitional cells. The role of a possible third input from the left atrium has not been investigated. Since the transition from atrial fibers to nodal fibers is gradual, it is very difficult to define the "beginning" of the AV node, and gross measurements of AV nodal length may be misleading. Histologically, the "end" of the AV node is equally difficult to define. At the site where macroscopically the AV node ends, at the point where the AV bundle penetrates into the membranous septum, typical nodal cells intermingle with His bundle cells. A conspicuous feature, found in all species studied, is the paucity of junctional complexes, most marked in the midnodal area. The functional counterpart of this is an increased coupling resistance between nodal cells. An electrophysiological classification of the AV nodal area, based on transmembrane action potential characteristics during various imposed atrial rhythms (rapid pacing, trains of premature impulses), into AN (including ANCO and ANL), N, and NH zones has been described by various authors for the rabbit heart. In those studies in which activation patterns, transmembrane potential characteristics, and histology have been compared, a good correlation has been found between AN and transitional cells, N cells and the area where transitional cells and cells of the beginning of the AV bundle merge with midnodal cells, and NH cells and cells of the AV bundle. Dead-end pathways correspond to the posterior extension of the bundle of lower nodal cells and to anterior overlay fibers. During propagation of a normal sinus beat, activation of the AN zone accounts for at least 25% of conduction time from atrium to His bundle, the small N zone being the main source of AV nodal delay. Cycle length-dependent conduction delay is localized in the N zone. Conduction block of premature atrial impulses can occur both in the N zone and in the AN zone, depending on the degree of prematurity. Several factors determining AV nodal conduction delay have been identified.(ABSTRACT TRUNCATED AT 400 WORDS)