ROLE OF CARDIAC MICROSTRUCTURE IN ARRHTHMIA GENERATION AND DEFIBRILATION IN THE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the importance of defibrillation therapy, understanding of mechanisms by which electric shocks halt life-threatening arrhythmias remains incomplete. While recent experimental advances have provided new characterizations of tissue responses to shocks, mechanistic inquiry into the success and failure of defibrillation is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles. The overall objective of this study is, by employing realistic 3D computer simulations, to bring a new level of understanding of the post-shock events in the heart that lead to the failure of the shock. Current models do not incorporate anatomical microheterogeneities, which could play an important role. Specifically, in this project we examine, in bidomain models of cardiac micro-structure, mechanisms underlying the ``isoelectric window", the quiescent period often preceding the first postshock activation following failed shocks.