Dynamic Mechanism for Initiation of Ventricular Fibrillation In Vivo

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...