The overall objective of this study is to determine the factors responsible for the rate-dependent conduction slowing induced by ischemia, the effect of drugs on the rate-dependent slowing and the effects of ischemia on the rate or use-dependent effects of the antiarrhythmic drugs. This study, which employes a model of low flow ischemia in the pig, continues ongoing studies in the Program Project evaluating the influence of drugs on ischemia and the influence of ischemia on the effects of drugs. This study is related to the central goal of the program in that it addresses the pathophysiology of the conduction slowing known to be a part of the ischemic process and the influence of drugs on this process. The study deals with the four interacting themes of the Program Project, namely; 1) the electrophysiology underlying sudden cardiac death, 2) the study of the ionic-electrical correlations in ischemia using ion selective electrodes, 3) the effects of rate on electrophysiologic properties and 4) the effects of cardio-active drugs. It specifically interacts with the other studies in group A which address the ionic and electrical interactions in acute ischemia, the single fiber studies in group B which address many of the same questions proposed in this project using microelectrode techniques, and the studies in group C dealing with the prospective identification of patients at risk for sudden cardiac death and their treatment with antiarrhythmic drugs. The project will utilize all core facilities, particularly the animal/electrode core and the computer core.
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