The long term goal of these studies is to obtain information that will provide better understanding of the electrophysiological mechanisms that sensitize the ischemic heart, or the heart damaged by infarction, to ventricular fibrillation and to learn the manner and extent to which antiarrhythmic drugs can influence this outcome. The overall objective is to reduce the incidence of sudden cardiac death. One group of experiments will be conducted on single ventricular myocytes isolated from canine or guinea pig heart and studied with voltage-clamp methods to identify specific effects of various classes of antiarrhythmic drugs and related compounds that will have predictable effects on impulse conduction in ischemic regions of the canine ventricle. The drugs will be administered to chronically instrumented dogs, with and without prior infarction, in which transient coronary occlusion can be made and in which electrograms can be recorded from the ischemic myocardium. The objective of these experiments is to determine what drug effects consistently modify impulse propagation in ischemic muscle to alter the incidence of ventricular fibrillation. Other experiments will be conducted on isolated preparations of canine cardiac muscle to develop rules for interpretation of the complex electrograms recorded from the heart during local ischemia. This information will aid in the interpretation of data obtained from the in situ heart.
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