): The central goal of the project is to clarify the mechanisms by which ventricular fibrillation (VF) is maintained.
Specific Aim 1 will determine how agents that uncouple excitation-contraction like diacetyl monoxime (DAM) or cytochalasin D (cyto-D) and/or the voltage-sensitive dye affect VF activation patterns. The effects of these mechanical uncoupling drugs will be examined by mapping pig hearts with surface electrogram recordings 1) in situ, 2) in isolated perfused hearts, 3) isolated perfused hearts with uncoupling drugs and 4) isolated and perfused hearts with uncoupling drugs and voltage sensitive dyes.
Specific Aim 2 will correlate the regions of propagation block during VF with static and dynamic repolarization properties. The study will determine if propagation block in optical mapping data of VF correlate with 1) areas of non-uniform dispersion of intrinsic action potential duration (APD) and 2) if rate-dependent repolarization instabilities cause APD oscillations of growing amplitude that eventually lead to block in VF.
Specific Aim 3 will determine the prevalent mode of propagation during VF and its relationship to block. The applicant will develop a method to record a complete epicardial map of activation using 2 cameras as in """"""""Panoramic Mapping"""""""" and will use novel algorithms to unambiguously characterize activation arising from (1) rotors, (2) wandering wavelets or (3) epicardial breakthrough. The data will differentiate between alternate hypothesized VF mechanisms. The project will test hypotheses relating block to the drift of rotors and the interaction of intramural reentry with the epicardial surface.
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