Bradycardia-Mediated Ventricular Electrical Remodeling

Bradycardic states are associated with myocardial electrical remodeling predisposing to potentially lethal ventricular tachydysrhythmias. We used a novel model of complete heart block (CHB) in the rabbit to test the hypothesis that ventricular activation rate is the primary determinant of early bradycardic electrical remodeling. Chronic endocardial right ventricular demand (VVI) pacing was applied at either the near-physiologic rate of 280 beats/min or at the bradycardic rate of 140 beats/min, beginning immediately after transcatheter radiofrequency AV node ablation. A third group of animals underwent sham ablation and served as non-paced, normal sinus rhythm controls. The major finding of this study was that electrical remodeling was established within 8 days of CHB induction in the bradycardic animals, but was not observed in either of the other 2 groups. Bradycardic animals had significant QT interval prolongation and biventricular downregulation of the delayed rectifier K+ currents, IKr and IKs. The Ca2+-independent transient outward K+ current, I_to, and the inwardly rectifying K+ current, I_K1, were unaffected. This paper highlights these findings in the context of a literature-based review of heart rate-dependent remodeling of the mammalian myocardium, summarizing the current state of knowledge and describing future challenges.