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Circulation Research. 2003
Published online before print October 16, 2003, doi: 10.1161/01.RES.0000101913.95604.B9
A more recent version of this article appeared on November 28, 2003
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Submitted on August 5, 2003
Revised on September 30, 2003
Accepted on October 7, 2003

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

Halina Dobrzynski ; Vladimir P. Nikolski ; Alexandre T. Sambelashvili ; Ian D. Greener ; Mitsuru Yamamoto ; Mark R. Boyett ; and Igor R. Efimov *

From the Department of Biomedical Engineering (H.D., V.P.N., A.T.S., I.R.E.), Case Western Reserve University, Cleveland, Ohio; School of Biomedical Sciences (H.D., I.D.G., M.Y., M.R.B.), University of Leeds, Leeds, UK.

* To whom correspondence should be addressed. E-mail: ire{at}case.edu.

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, If, by 2 mmol/L Cs+ increased the AV junctional rhythm cycle length from 611±84 to 949±120 ms (mean±SD, n=6, P<0.001). Immunohistochemical investigation showed that the principal If 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 • electrophysiology • surgery • arrhythmia • imaging




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