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(Circulation. 2008;118:1123-1129.)
© 2008 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Dynamic Mechanism for Initiation of Ventricular Fibrillation In Vivo

Anna R.M. Gelzer, DVM^*; Marcus L. Koller, MD^*; Niels F. Otani, PhD; Jeffrey J. Fox, PhD; Michael W. Enyeart, MS; Giles J. Hooker, PhD; Mark L. Riccio, MSEE; Carlo R. Bartoli, BS; Robert F. Gilmour, Jr, PhD

From the Departments of Clinical Sciences (A.R.M.G.) and Biomedical Sciences (N.F.O., M.W.E., M.L.R., C.R.B., R.F.G.), College of Veterinary Medicine, and Department of Statistical Science (G.J.H.), Cornell University, Ithaca, NY; Department of Cardiology, Center of Cardiovascular Medicine, Bad-Neustadt, Germany (M.L.K.); and Gene Network Sciences, Ithaca, NY (J.J.F.).

Correspondence to Anna Gelzer, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail arg9{at}cornell.edu

Received June 9, 2006; accepted July 11, 2008.

Background— Dynamically induced heterogeneities of repolarization may lead to wave-front destabilizations and initiation of ventricular fibrillation (VF). In a computer modeling study, we demonstrated that specific sequences of premature stimuli maximized dynamically induced spatial dispersion of refractoriness and predisposed the heart to the development of conduction block. The purpose of this study was to determine whether the computer model results pertained to the initiation of VF in dogs in vivo.

Methods and Results— Monophasic action potentials were recorded from right and left ventricular endocardium in anesthetized beagle dogs (n=11) in vivo. Restitution of action potential duration and conduction time and the effective refractory period after delivery of the basic stimulus (S₁) and each of 3 premature stimuli (S₂, S₃, S₄) were determined at baseline and during verapamil infusion. The effective refractory period data were used to determine the interstimulus intervals for a sequence of 4 premature stimuli (S₂S₃S₄S₅=CL_VF) for which the computer model predicted maximal spatial dispersion of refractoriness. Delivery of CL_VF was associated with discordant action potential duration alternans and induction of VF in all dogs. Verapamil decreased spatial dispersion of refractoriness by reducing action potential duration and conduction time restitution in a dose-dependent fashion, effects that were associated with reduced inducibility of VF with CL_VF.

Conclusion— Maximizing dynamically induced spatial dispersion of repolarization appears to be an effective method for inducing VF. Reducing spatial dispersion of refractoriness by modulating restitution parameters can have an antifibrillatory effect in vivo.

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CLINICAL PERSPECTIVE

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