Mechanisms for Maintenance of Ventricular Fibrillation

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The broad objectives of this project are to elucidate the mechanisms by which ventricular fibrillation (VF) is maintained and to develop novel treatment modalities. The ultimate goal is to prevent sudden cardiac death. Specific Aim 1. Test for the presence of sustained reentry in fibrillating slabs of swine ventricle. One of the largest current controversies in VF research is whether VF is driven by a small number of sustained reentrant sources or by the continual fragmentation of short-lived wavefronts. This project will test for the presence of sustained reentry by combining epicardial and intramural electrical cardiac mapping in slabs of swine myocardium. Specific Aim 2. Map propagation in monolayers of cultured myocytes to test for the effects of surface and fiber curvature. During VF, wavefronts experience local propagation block and fragment when they encounter regions with properties that differ from their surroundings. Such heterogeneity has classically been thought to be due to differences in cellular properties. Recent theoretical work suggests that even in homogeneous tissue, heterogeneity can result solely from the curvature of the tissue or of the muscle fibers. This project will test for the presence of these phenomena in monolayers of cultured myocytes Specific Aim 3. Using novel technology to map and parameterize VF patterns, test whether propagation block is due to fixed or to dynamic heterogeneities. It has recently been proposed that the heterogeneities leading to propagation block during VF are dynamic, i.e., induced by the activation/recovery pattern, and not spatially fixed. Using panoramic optical maps of fibrillating swine hearts and novel pattern analysis algorithms, this project will determine whether block during VF is due to static heterogeneities, dynamic heterogeneities, or a combination of these factors. Specific Aim 4. Test the ability of novel analog control circuits to capture fibrillating myocardium With pacing stimuli. Previous work has shown that pacing stimuli can capture regions of'fibrillating myocardium. A novel class of analog circuits will be used to control the delivery of pacing stimuli. The ultimate goal is to capture the entire heart and terminate fibrillation. This project will develop single anld multisite pacing circuits and evaluate their performance using panoramic optical mapping of isolated perfused swine hearts.