A low probability for successful resuscitation (about 50%), postshock arrhythmias including shock-induced refibrillation, S-T segment changes, and other signs of dysfunction are often observed following clinical defibrillation. This dysfunction, which is dependent on the waveform and intensity of the shock, is caused in part, by a shock-induced, prolonged depolarization of the myocardial cell membrane. The probability for successful resuscitation in animal models is predicted by the """"""""safety factor"""""""" (ratio between dysfunction-producing intensities and excitation or defibrillation threshold shock intensities) of the defibrillating waveform. This study examines mechanisms underlying defibrillation and postshock dysfunction at the cellular level. Its goals are to confirm the safety factor concept, which is based on the hypothesis that mechanisms underlying defibrillation and shock-induced dysfunction differ, and to develop a triphasic waveform to increase safety factor. This waveform, which consists of a """"""""conditioning prepulse"""""""", a """"""""defibrillating pulse"""""""", and a """"""""healing postpulse"""""""" is expected to increase safety factor by 300% over present clinical waveforms. Initial studies will be carried out in cultured myocardial cells using photocell mechanograms, and intracellular microelectrode techniques, as well as optical techniques for measurement of membrane potential distribution and intracellular calcium. Results from experimental studies will be incorporated into theoretical models to explain defibrillation mechanisms in terms of dynamic membrane characteristics and electromagnetic field theory. The triphasic waveform developed in these studies will be tested using the dog model for transthoracic defibrillation. The results of these experiments will suggest specific modifications to defibrillation procedures which are based on a firm physiological understanding of the actions of the strong electric field on the myocardial cell. In addition to yielding information of potentialy significant clinical interest, these studies also will increase our understanding of the fundamental mechanisms underlying interactions of external electric field with biological systems.
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