Dynamically-Induced Spatial Dispersion of Repolarization and the Development of VF in an Animal Model of Sudden Death

Spatial dispersion of refractoriness and discordant action potential duration (APD) alternans, resulting in local conduction block, have been shown to cause wavebreak that can lead to ventricular fibrillation (VF). Previously, we developed a theory, based on action potential restitution functions, that predicts when the requisite conduction block can be created through a series of premature beats. The theory was applied successfully to normal beagle dogs; however, restitution functions in these animals were similar, both between right and left ventricles in a given animal and across animals. Consequently, for the present study we tested the theory on a population of German shepherds that, due to inherited cardiac abnormalities, presented with a wide variation of APD restitution functions. We found that the theory, when applied to restitution functions determined individually for each animal, reliably generated premature stimulation predictions that frequently resulted in the induction of VF in in vivo experiments.