Sudden cardiac death due to ventricular fibrillation is a major cause of mortality in the United States leading to over 400,000 deaths annually. Many cases of ventricular fibrillation occur suddenly and outside of the hospital where response times may be prolonged. The probability of successfully converting ventricular fibrillation to normal sinus rhythm decreases significantly with fibrillation duration so that after approximately seven minutes, only 60% of episodes are converted to any other rhythm. Since half of these conversions are to ventricular standstill leading to death, only 30% of patients are converted to a perfusing rhythm resulting in survival. If fibrillation could be successfully converted to normal sinus rhythm in these patients, new developments in treating ischemia could allow normal recovery. This proposal suggests the hypothesis that electrophysiological characteristics of the heart change after approximately one minute of fibrillation so that mechanisms underlying defibrillation differ from those which underlie defibrillation following the short fibrillation durations of less than 30 seconds typical of implantable defibrillators. Following short fibrillation durations, cells are restimulated before complete repolarization from their previous action potential. Therefore, defibrillation is produced by interaction of the shock with cells during their action potential. The resulting response prolongs the total refractory period and prevents incoming fibrillation wavefronts from propagating, thereby terminating fibrillation. Following long fibrillation durations, most ventricular cells are found in diastole, but are depolarized due to the preceding ischemia. Therefore, defibrillation is produced by interaction of the shock with cells during diastole. The resulting response produces synchronized action potentials throughout the heart which synchronizes refractory periods and also produces a perfusing beat. The goals of this project are to test this hypothesis and to develop new defibrillation and pacing waveforms to improve efficacy of defibrillation and reduce postshock standstill following fibrillation durations ranging from 30 seconds to five minutes. The project will use the isolated bi-ventricular working rabbit heart model. Epicardial and endocardial monophasic action potentials, ventricular and aortic pressures, and electrocardiograms will be correlated with defibrillation thresholds, duration of postshock standstill, and fibrillation duration. Results are expected to suggest improvements in defibrillation and resuscitation techniques which will significantly improve probability of survival from out-of-hospital cardiac arrest.
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