Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart

Aim: To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. Methods: Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi‐electrode plaque containing 256 electrodes and a spectral method were used to obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated hearts was determined as an electrophysiological parameter of training. In vivo heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide synthase were also determined in some animals as electrophysiological and biochemical markers of training respectively. Results: VERP and VFRP were longer in the trained group than in the control group. The mean DF of VF was lower in the trained group than in the control group. Despite the fact that training did not significantly modify the AERP, it tended to be longer in the trained group (P = 0.09). Conclusion: Training seems to increase the electrical stability of ventricular myocardium. As the electrophysiological modifications were exhibited in hearts not submitted to extrinsic nervous system or humoral influences, they are, at least in part, intrinsic modifications. These electrophysiological data also suggest that training could protect against reentrant ventricular arrhythmias.     

Atrial automaticity and atrioventricular conduction in athletes: contribution of autonomic regulation

Little is known about the sinoatrial automatism and atrioventricular conduction of trained individuals who present a normal resting electrocardiogram. We used transesophageal atrial stimulation, a minimally invasive technique, to evaluate aerobically trained athletes (n=10) and sedentary individuals (n=10) with normal resting electrocardiograms, to test the hypothesis that parasympathetic tone, as detected by heart rate variability, could be associated with changes in sinoatrial automatism and atrioventricular conduction. Corrected sinus node recovery time tended to be longer in athletes than in sedentary individuals, but this difference did not reach statistical significance. The Wenckebach point occurred at a lower rate in athletes than in the controls. Over a 24-h period of measurement, the mean RR interval was longer in the athletes than in the sedentary individuals. The mean square root of successive differences (rMSSD) tended to be higher in athletes than in controls, but this difference did not reach statistical significance. There was a moderate correlation (r=0.48, P < 0.05) between the index of atrioventricular conduction, the rate at the Wenckebach point, and the logarithmically transformed rMSSD. Thus, as a corollary to its effects on the sinus node, where increased parasympathetic tone, decreased sympathetic tone, and non-autonomic components may contribute to sinus bradycardia, it is possible that athletic training may also induce intrinsic adaptations in the conduction system, which could contribute to the higher prevalence of atrioventricular conduction abnormalities observed in athletes. Accepted: 2 January 2000     

Can local ventricular fibrillation interval predict ventricular refractory period in human hearts?

Assessment of the spatial dispersion of ventricular refractory periods has become an important part of electrophysiological study in both experimental and clinical settings, because inhomogeneity of ventricular refractoriness is associated with an increased risk of life-threatening ventricular arrhythmias. Previous animal studies in dog and sheep have demonstrated that local ventricular fibrillation (VF) intervals measured from the heart surface correlate well with the ventricular effective refractory periods measured from the same ventricular sites. We hypothesise that local VF intervals may also predict the ventricular refractory periods in human hearts, hence, can be used to assess the spatial dispersion of refractoriness and to predict the risk of ventricular arrhythmias.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VF rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VF. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics.

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VT rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

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.     

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole—methods and preliminary results

SUMMARY  Twelve patients (aged 48 ± 12 y) with ventricular asystole of >3s due to complete atrioventricular (AV) block ( n = 8), sinoatrial (SA) block or sinus node arrest ( n = 3) or both ( n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg^-1). Ventricular asystole lasted for 5.9 ± 2.8 s (range 3.1–13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59–63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.     

Histological examination of the potential arrhythmic substrates in the setting of Ebstein’s malformation

Cardiac arrhythmias, notably Wolff-Parkinson-White syndrome, are known to represent a major issue in patients with Ebstein’s malformation of the tricuspid valve. Abnormal conducting circuits, however, can also be produced by pathways extending either from the atrioventricular node or the ventricular components of the atrioventricular conduction axis, direct to the crest of the muscular ventricular septum. We hoped to provide further information on the potential presence of such pathways by investigations of six autopsied examples of Ebstein’s malformation. All were studied by histological sectioning on the full extent of the atrioventricular conduction axis, with limited sectioning of the right atrioventricular junction supporting the inferior and antero-superior leaflets of the deformed tricuspid valve. We used the criteria established by Aschoff (Verhandlungen der Deutschen Gesellschaft für Pathologie, 14, 1910, 3) and Mönckeberg (Verhandlungen der Deutschen Gesellschaft für Pathologie, 14, 1910, 64) over a century ago to define abnormal connections across the atrioventricular junctions, as these definitions retain their validity for the identification of gross myocardial connections across the insulating tissues of the atrioventricular junctions. In one specimen, we found two discrete accessory myocardial connections across the parietal right atrioventricular junction. In all of the hearts, we found so-called nodoventricular connections, and in one heart we also observed a well-formed connection originating from the penetrating atrioventricular bundle. In addition to accessory myocardial connections across the parietal right atrioventricular junction, therefore, our histological findings demonstrate a potential role for direct connections between the atrioventricular conduction axis and the ventricular myocardium in the setting of Ebstein’s malformation.     

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.     

核纤层蛋白A、转录因子TBX3、缝隙连接蛋白43表达与小鼠胚胎心发育

目的 探讨小鼠胚胎心脏工作心肌和传导系心肌在形态发生和分化过程中核纤层蛋白A（lamin A）、转录因子TBX3、缝隙连接蛋白43（Cx43）的表达特点。
方法 用抗α-平滑肌肌动蛋白（α-SMA）、抗心肌肌球蛋白重链（MHC）、抗α-横纹肌肌动蛋白（α-SCA）、抗胰岛因子1（ISL-1）、抗Cx43、抗lamin A和抗转录因子TBX3,对46只胚龄8～15d小鼠胚胎心脏连续石蜡切片进行免疫组织化学及免疫荧光染色。 结果 胚龄9d,TBX3在原始心管的表达集中在房室管壁。10d始,TBX3阳性的表达逐渐从房室管壁沿着静脉瓣延续至窦房结、右心房背侧壁和房间隔。胚龄12～13d,TBX3阳性表达结构构成了中枢传导系雏形,包括窦房结、左右静脉瓣、房间隔、房室管、房室结和房室束。Cx43首先在胚龄9d的左心室腹侧壁和部分小梁心肌出现弱阳性表达,随着发育,Cx43逐渐在TBX3阴性的心房、心室工作心肌表达。Lamin A首先出现在10d房室管心内膜垫间充质细胞和左心室部分小梁心肌,随后在右心室小梁心肌出现,至胚龄15d,心室和心房小梁心肌及房室瓣均可见lamin A阳性表达,但致密心肌和中枢传导系心肌持续呈阴性表达。 结论 中枢传导系统雏形在小鼠胚龄13d形成,呈TBX3阳性,Cx43阴性的互补性表达。致密心肌和中枢传导系心肌在15d仍为lamin A表达阴性,说明此部分心肌分化成熟较晚。     

Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins,superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well-known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti-desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts.     

Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is important for the control of cardiac dynamics, especially in the conduction system. Our objective was to assess the relative distribution of autonomic nerves in the pig heart, focusing initially on the conduction system but addressing also the myocardium, endocardium and epicardium (see Crick et al. 1999). Quantitative immunohistochemical and histochemical techniques were adopted. All regions of the conduction system possessed a significantly higher relative density of the total neural population immunoreactive for the general neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjacent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventricular node, and the penetrating atrioventricular bundle. A differential pattern of PGP 9.5-immunoreactive innervation was present within the atrioventricular node and between the components of the ventricular conduction tissues, the latter being formed by an intricate network of Purkinje fibres. Numerous ganglion cell bodies were present in the peripheral regions of the sinus node, in the tissues of the atrioventricular groove, and even in the interstices of the compact atrioventricular node. Acetylcholinesterase (AChE)-containing nerves were the dominant subpopulation observed, representing 60–70% of the total pattern of innervation in the nodal tissues and penetrating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most abundant neural subpopulation, representing 37% of the total pattern of innervation in the compact atrioventricular node compared with 25% in the transitional nodal region. A minor population of ganglion cell bodies within the atrioventricular nodal region displayed TH immunoreactivity. The dominant peptidergic nerve supply possessed immunoreactivity for neuropeptide Y (NPY), which displayed a similar pattern of distribution to that of TH-immunoreactive nerve fibres. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves represented 8–9% of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14–19% in the bundle branches. Somatostatin-immunoreactive nerve fibres were relatively sparse (4–13% of total innervation) and were most abundant in the nodes, especially the compact atrioventricular node. The total pattern of innervation of the porcine conduction system was relatively homogeneous. A substantial proportion of nerve fibres innervating the nodal tissues could be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular conduction tissues was similar to that observed in the bovine heart, but markedly different to that of the human heart. It is important that we are aware of these findings in view of the future use of transgenic pig hearts in human xenotransplantation.     

Regional frequency variation during human ventricular fibrillation

Quantifying the regional frequency variation in ventricular fibrillation (VF) may lead to focal strategies in treating human VF. We hypothesized that during human VF there are quantifiable regional frequency variations in the ventricles and they relate to underlying fixed myocardial substrate. In eight myopathic human hearts, we studied 35 VF episodes. The electrograms during VF were acquired simultaneously from the epicardium and endocardium using 2 electrode arrays each consisting of 112 electrodes. Regional characterization was performed using a ratio parameter derived from the dominant frequency analysis of the electrograms. The findings were related to the anatomical substrate using bipolar voltage maps. The results of the analysis indicate that LV had a larger dominant frequency (DF) span than RV (p=0.0111) while there was no significant difference (p=0.1488) in the DF span between LV freewall (FW) and septum (SE). Correlation of areas of abnormal myocardium with the dominant frequency feature matched only in 50% of the cases indicating that ion channel heterogeneity and time-varying physiological factors may play an important role in maintaining VF.     

The Relative Role of Refractoriness and Source–Sink Relationship in Reentry Generation during Simulated Acute Ischemia

During acute myocardial ischemia, reentrant episodes may lead to ventricular fibrillation (VF), giving rise to potentially mortal arrhythmias. VF has been traditionally related to dispersion of refractoriness and more recently to the source–sink relationship. Our goal is to theoretically investigate the relative role of dispersion of refractoriness and source–sink mismatch in vulnerability to reentry in the specific situation of regional myocardial acute ischemia. The electrical activity of a regionally ischemic tissue was simulated using a modified version of the Luo-Rudy dynamic model. Ischemic conditions were varied to simulate the time-course of acute ischemia. Our results showed that dispersion of refractoriness increased with the severity of ischemia. However, no correlation between dispersion of refractoriness and the width of the vulnerable window was found. Additionally, in approximately 50% of the reentries, unidirectional block (UDB) took place in cells completely recovered from refractoriness. We examined patterns of activation after premature stimulation and they were intimately related to the source–sink relationship, quantified by the safety factor (SF). Moreover, the isoline where the SF dropped below unity matched the area where propagation failed. It was concluded that the mismatch of the source–sink relationship, rather than solely refractoriness, was the ultimate cause of the UDB leading to reentry. The SF represents a very powerful tool to study the mechanisms responsible for reentry.     

Autonomic innervation of the human cardiac conduction system: changes from infancy to senility--an immunohistochemical and histochemical analysis

In order to study the changes in the pattern of autonomic innervation of the human cardiac conduction system in relation to age, the innervation of the conduction system of 24 human hearts (the age of the individuals ranged from newborn to 80 years), freshly obtained at autopsy, was evaluated by a combination of immunofluorescence and histochemical techniques. The pattern of distribution and density of nerves exhibiting immunoreactivity against protein gene product 9.5 (PGP), a general neural marker, dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), indicators for presumptive sympathetic neural tissue, and those demonstrating positive acetylcholinesterase (AChE) activity, were studied. All these nerves showed a similar pattern of distribution and developmental changes. The density of innervation, assessed semiquantitatively, was highest in the sinus node, and exhibited a decreasing gradient through the atrioventricular node, penetrating and branching bundle, to the bundle branches. Other than a paucity of those showing AChE activity, nerves were present in substantial quantities in infancy. They then increased in density to a maximum in childhood, at which time the adult pattern was achieved and then gradually decreased in density in the elders to a level similar to or slightly less than that in infancy. In contrast, only scattered AChE-positive nerves were found in the sinus and atrioventricular nodes, but were absent from the bundle branches of the infant heart, whereas these conduction tissues themselves possessing a substantial amount of pseudocholinesterase. During maturation into adulthood, however, the conduction tissues gradually lost their content of pseudocholinesterase but acquired a rich supply of AChE-positive nerves, comparable in density to those of DBH and TH nerves. The decline in density of AChE-positive nerves in the conduction tissues in the elders was also similar to those of DBH and TH nerves. Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transition into a sympathetic and parasympathetic codominance in adulthood, correlate well with the physiologic alterations known to occur in cardiac rate during postnatal development. The finding of reduction in density of innervation of the conduction tissue with ageing is also in agreement with clinical and electrophysiological findings such as age-associated reduction in cardiac response to parasympathetic stimulation. Finally, our findings also support the hypothesis that, in addition to the para-arterial route, the parafascicular route of extension along the conduction tissue constitutes another pathway for the innervation of the conduction system of the human heart during development.     

Autonomic innervation of the human cardiac conduction system: Changes from infancy to senility—An immunohistochemical and histochemical analysis

In order to study the changes in the pattern of autonomic innervation of the human cardiac conduction system in relation to age, the innervation of the conduction system of 24 human hearts (the age of the individuals ranged from newborn to 80 years), freshly obtained at autopsy, was evaluated by a combination of immunofluorescence and histochemical techniques. The pattern of distribution and density of nerves exhibiting immunoreactivity against protein gene product 9.5 (PGP), a general neural marker, dopamine β‐hydroxylase (DBH) and tyrosine hydroxylase (TH), indicators for presumptive sympathetic neural tissue, and those demonstrating positive acetylcholinesterase (AChE) activity, were studied. All these nerves showed a similar pattern of distribution and developmental changes. The density of innervation, assessed semiquantitatively, was highest in the sinus node, and exhibited a decreasing gradient through the atrioventricular node, penetrating and branching bundle, to the bundle branches. Other than a paucity of those showing AChE activity, nerves were present in substantial quantities in infancy. They then increased in density to a maximum in childhood, at which time the adult pattern was achieved and then gradually decreased in density in the elders to a level similar to or slightly less than that in infancy. In contrast, only scattered AChE‐positive nerves were found in the sinus and atrioventricular nodes, but were absent from the bundle branches of the infant heart, whereas these conduction tissues themselves possessing a substantial amount of pseudocholinesterase. During maturation into adulthood, however, the conduction tissues gradually lost their content of pseudocholinesterase but acquired a rich supply of AChE‐positive nerves, comparable in density to those of DBH and TH nerves. The decline in density of AChE‐positive nerves in the conduction tissues in the elders was also similar to those of DBH and TH nerves. Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transition into a sympathetic and parasympathetic codominance in adulthood, correlate well with the physiologic alterations known to occur in cardiac rate during postnatal development. The finding of reduction in density of innervation of the conduction tissue with ageing is also in agreement with clinical and electrophysiological findings such as age‐associated reduction in cardiac response to parasympathetic stimulation. Finally, our findings also support the hypothesis that, in addition to the para‐arterial route, the parafascicular route of extension along the conduction tissue constitutes another pathway for the innervation of the conduction system of the human heart during development. Anat Rec 264:169–182, 2001. © 2001 Wiley‐Liss, Inc.     

Autonomic boundary conditions for ventricular fibrillation and their implications for a novel defibrillation technique

The sympathetic and parasympathetic divisions of the autonomic nervous system modulate cardiac rhythm and the probability of arrhythmia occurrence. Both increased sympathetic drive and hypoxia increase the likelihood for ventricular fibrillation (VF). Vagus nerve stimulation (VNS) can protect from fatal arrhythmias via cholinergic and nitrergic action. We sought to determine boundary conditions for VF and defibrillation by autonomic manipulations accompanied or not by hypoxic changes in urethane-anesthetized rats. VF was induced with (1) vagotomy, (2) systemic high-dose (>15?mg/kg) isoproterenol, and (3) hypoxemia. When VNS (50?Hz) produced cardiac standstill, it converted every VF episode (59/59). A nitric oxide synthase inhibitor did not reduce VNS efficacy (13/14 episodes converted), but addition of atropine reduced VNS efficacy (11/27 episodes converted). VF can be induced by autonomic derangements only under constrained conditions, including sympathetic over-activation, reduced parasympathetic input, and hypoxemia. VNS can provide an alternative method to defibrillate via its cholinergic action.     

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.     

Three-dimensional visualization of the bovine cardiac conduction system and surrounding structures compared to the arrangements in the human heart

In the human heart, the atrioventricular node is located toward the apex of the triangle of Koch, which is also at the apex of the inferior pyramidal space. It is adjacent to the atrioventricular portion of the membranous septum, through which it penetrates to become the atrioventricular bundle. Subsequent to its penetration, the conduction axis is located on the crest of the ventricular septum, sandwiched between the muscular septum and ventricular component of the membranous septum, where it gives rise to the ramifications of the left bundle branch. In contrast, the bovine conduction axis has a long non-branching component, which penetrates into a thick muscular atrioventricular septum having skirted the main cardiac bone and the rightward half of the non-coronary sinus of the aortic root. It commonly gives rise to both right and left bundle branches within the muscular ventricular septum. Unlike the situation in man, the left bundle branch is long and thin before it branches into its fascicles. These differences from the human heart, however, have yet to be shown in three-dimensions relative to the surrounding structures. We have now achieved this goal by injecting contrast material into the insulating sheaths that surround the conduction network, evaluating the results by subsequent computed tomography. The fibrous atrioventricular membranous septum of the human heart is replaced in the ox by the main cardiac bone and the muscular atrioventricular septum. The apex of the inferior pyramidal space, which in the bovine, as in the human, is related to the atrioventricular node, is placed inferiorly relative to the left ventricular outflow tract. The bovine atrioventricular conduction axis, therefore, originates from a node itself located inferiorly compared to the human arrangement. The axis must then skirt the non-coronary sinus of the aortic root prior to penetrating the thicker muscular ventricular septum, thus accounting for its long non-branching course. We envisage that our findings will further enhance comparative anatomical research.     

Detection of ventricular fibrillation using empirical mode decomposition and Bayes decision theory

Ventricular fibrillation (VF) is the most serious variety of arrhythmia which requires quick and accurate detection to save lives. In this paper, we propose an empirical mode decomposition (EMD) based algorithm for VF detection. The intrinsic mode functions (IMFs) of VF are orthogonal whereas the lower order IMFs of normal sinus rhythm (NSR) are not. The orthogonality indices derived from the first three consecutive intrinsic mode functions (IMFs) of NSR and VF are used for their discrimination. The proposed technique is applied to the MIT-BIH arrhythmia database. The accuracy of detection of VF is 99.70% for a window length of 3 s. This early estimate of VF may be useful in emergency cases where defibrillators are to be applied. Comparative results with the existing methods in terms of quality parameters and integrated receiver operating characteristic (IROC) are presented.