The long-term objective of this work is to increase our fundamental understanding of ventricular fibrillation by mapping cardiac activation. The first specific aim is to determine where and how the activation fronts arise that initiate ventricular fibrillation, whether from the endocardium, lateral border zone, or epicardium and whether by one or more re-entrant pathways or ectopic foci. This will be done by recording simultaneously from 124 electrodes distributed transmurally throughout the walls of the left and right ventricles in animal models of conditions thought to occur clinically, including acute ischemia, acute ischemia followed by reperfusion, old infarction, and acute ischemia superimposed on old infarction. Studies will be performed both in sedated, opened-chest animals and in awake, closed-chest animals. Three dimensional computer displays will be improved to show the complex spread of activation during ventricular fibrillation. The hypotheses will be tested that ventricular fibrillation (1) is initiated by and (2) is maintained by activation emanating from the Purkinje cells in the subendocardium. Ventricular fibrillation will be recorded in patients undergoing cardiac surgery for life-threatening arrhythmias. Fibrillation can occur during the standard protocols for treating these patients. Activation sequences recorded during ventricular fibrillation in humans will be compared to those in animals to test the validity of the conclusions obtained from the animal studies. The second specific aim is to determine why fibrillation arises where and how it does. The three-dimensional distribution of viable and infarcted tissue, injury potentials, T wave potentials, extracellular K concentration and extracellular pH will be quantified. Conduction velocity, refractory periods, and levels of alpha and beta adrenoreceptors will also be determined. All of these variables in the region giving rise to fibrillation will be compared to regions elsewhere in ischemic or infarcted tissue that are not arrhythmogenic. The third specific aim is to determine the amount and location of myocardium that is directly depolarized by a defibrillation shock. The computer assisted mapping system to be used in this work can record within 5 msec of a defibrillation shock without amplifier saturation. With this mapping system, the optimum size, shape, and location of internal and external electrodes and the optimum wave form will be found for defibrillation. The hypothesis will be tested that multiple, closely-spaced small shocks can better halt fibrillation than a single large shock. The basic understanding of the fundamental mechanisms of ventricular fibrillation gained from this work should aid in the development of rational therapy to prevent and halt the number one health problem in the United States today.
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