While reentry is the mechanism of defibrillation failure for shocks well below the defibrillation threshold (DFT), recent optical and 3-dimensional electrical mapping studies indicate that the mechanism of failure of near DFT strength shocks in normal hearts after 10 sec of ventricular fibrillation (VF) is the induction of at least 3 rapidly activating post-shock cycles arising from a focus where the shock field is weak. Thus it is crucial to understand how and why these focal rapid cycles arise and if the roles of the focal initiator and of the myocardial substrate in which the rapid cycles induce reentry are altered by cardiac disease or extended VF. This application proposes to accomplish three significant aims through the use of electrical and optical mapping to achieve this goal.
Specific aim 1 : Determine if at least 3 rapid focal ectopic cycles are necessary for the failure of near-DFT strength shocks in the presence of cardiac disease or long lasting VF. Because of the electrophysiologic alterations caused by old myocardial infarction, rapid pacing induced heart failure and longer lasting VF, it is possible that under these conditions fewer than 3 focal rapid cycles are required for defibrillation failure or even that foci are no longer observed.
Specific aim 2 : Determine the mechanism by which the focal cycles arise. Hypotheses will be tested that the rapid cycles are caused by delayed afterdepolarizations, early afterdepolarizations (EADs) or microreentry.
Specific aim 3 : Determine the mechanisms which cause the rapid focal cycles to arise in a particular cardiac location. The majority of foci in pigs arise within 4 mm of the epicardium. Hypotheses will be tested that the foci are located in this region because it is (1) within the M cell layer, (2) the boundary between the M cell and subepicardial layers, (3) the farthest extension of the Purkinje fibers, or (4) where the shock electric field is weakest. It is hoped that the basic knowledge gained about defibrillation mechanisms through these studies will lead to the improvement of defibrillation in patients.
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