Site of Origin and Molecular Substrate of Atrioventricular Junctional Rhythm in the Rabbit Heart

Abstract

Abstract-During failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker.The position of the leading pacemaker site during AV junctional rhythm is debated. In this study, we present evidence from high-resolution fluorescent imaging of electrical activity in rabbit isolated atrioventricular node (AVN) preparations that, in the majority of cases (11 out of 14), the AV junctional rhythm originates in the region extending from the AVN toward the coronary sinus along the tricuspid valve (posterior nodal extension, PNE). Histological and immunohistochemical investigation showed that the PNE has the same morphology and unique pattern of expression of neurofilament160 (NF160) and connexins (Cx40, Cx43, and Cx45) as the AVN itself. Block of the pacemaker current, I f , by 2 mmol/L Cs ϩ increased the AV junctional rhythm cycle length from 611Ϯ84 to 949Ϯ120 ms (meanϮSD, nϭ6, PϽ0.001). Immunohistochemical investigation showed that the principal I f channel protein, HCN4, is abundant in the PNE. As well as the AV junctional rhythm, the PNE described in this study may also be involved in the slow pathway of conduction into the AVN as well as AVN reentry, and the predominant lack of expression of Cx43 as well as the presence of Cx45 in the PNE shown could help explain its slow conduction. Key Words: ablation Ⅲ electrophysiology Ⅲ surgery Ⅲ arrhythmia Ⅲ imaging S ince Tawara's discovery of the atrioventricular node (AVN) nearly a century ago, 1 anatomists and electrophysiologists have established that the AVN is the only conduction pathway between the atria and ventricles in the normal heart. 2 The AVN has unique slow and frequencydependent conduction properties. 2 Under normal physiological conditions, the AVN determines the appropriate frequency-dependent delay of conduction between the atria and ventricles and, during atrial fibrillation, the AVN filters high-frequency excitation, thus protecting the ventricular myocardium. 3 The AVN has dual inputs (fast and slow pathways) from the atrial myocardium and this may be the substrate for AVN reentry. 4,5 The AVN also has pacemaking ability: during failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker, although the position of the leading pacemaker site is debated. 6,7 Recent application of fluorescent imaging with voltagesensitive dyes 5,8 -12 has provided new insights into the electrophysiology of the AV junction. With fluorescent imaging, we have recently shown how the fast and slow pathways of conduction support normal conduction, 9 AVN echo, 5 and AVN reentry. 12 Application of immunohistochemical imaging has shown that the expression of ion channels 13 and gap junction channel isoforms 14,15 can explain the electrophysiology of the AVN. In particular, a lack of or a low density of Na ϩ channels in the compact node (CN) can explain the slow upstroke and low amplitude of the action potential in CN. 13 Similarly, in CN, a lack of or a low density of low impedance isoforms of gap...

Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node

“…Furthermore, during high atrial heart rates, e.g., atrial fibrillation, the slow AV-nodal conductivity preserves the direct impulse transition to the ventricles, thus protecting the ventricular myocardium from the induction of ventricular arrhythmias like ventricular tachycardia or ventricular fibrillation (30). The factors responsible for this essential retardation of impulse propagation on AV-nodal level were largely unclear.…”

Three‐dimensional anatomy of the conduction system of the early embryonic rabbit heart

“…Antibodies against the neurofilament NAPA-73 have been localized to regions consistent with early conduction system in the ten somite embryonic chick heart (Ciment, 1990). Furthermore, the relationship to impulse conducting cells of the conduction system has been directly confirmed with electrophysiologic recording in the adult rabbit (Dobrzynski et al, 2003(Dobrzynski et al, , 2005). The rabbit embryo, then, is an ideal model for the visualization of the atrial and ventricular components of the normal mammalian cardiac conduction system.…”

Connexin-Mediated Cardiac Impulse Propagation: Connexin 30.2 Slows Atrioventricular Conduction in Mouse Heart

“…In addition, the relatively long refractory period of the AV-nodal cells and the dependence of the refractory period and of the conduction velocity on the frequency of excitation limit the maximum number of impulses within a given period that can be transmitted to the ventricles (Meijler and Janse 1988). Thus, the AV node filters high atrial frequencies during atrial fibrillation and therefore protects the ventricular myocardium against the transmission of atrial tachyarrhythmias (Dobrzynski et al 2003). Slow AV-nodal conduction under pathophysiologic conditions can also lead to the generation of life-threatening reentry tachycardias.…”

“…In human hearts, the formation of dual pathways with different conduction velocities (slow and fast) has been described as facilitating the development of local reentry circuits that can result in AV-nodal reentry tachycardia (Efimov et al 2004). In rabbit, dual-pathway conduction in the AV node was observed, and the slow pathway was thought to be located in the posterior nodal extension and Cx45 positive (Dobrzynski et al 2003). So far, there are no reports regarding slow and fast pathways in the mouse heart.…”