MYOCARDIAL ENERGY METABOLISM-EFFECT OF ETHANOL

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The long-range objective of this project will be to establish the relationship between ethanol-elicited alterations in myocardial energy metabolism and ethanol-related degenerative changes in the myocardium. An immediate objective is to establish the rat as an animal model for alcohol-induced cardiac disease. Rats will be fed ethanol diets which vary in their lipid and caloric content. The efficacy of these diets to give rise to alcohol-induced cardiac disease will be established. Criteria for pathology include distortion of mitochondria and sarcoplasmic reticulum, and degeneration of myofibrils as detected by electron microscopy. In addition to the ultrastructure studies, the tissue will be analyzed for adenine nucleotide, creatine, and creatine phosphate concentrations to evaluate its energy state. Isolated mitochondria will be assayed for their ability to catalyze oxidative phosphorylation. These initial measurements will be made in order to follow the progression of ethanol-related alterations in myocardial energy metabolism under different dietary regimens. Upon establishing an ethanol-containing diet that gives rise to degenerative changes in myofibrils, studies will be carried out to assess the degree to which ethanol feeding affects the mitochondrial-associated oxidative phosphorylation system. Previously published studies indicate that the ability of cardiac mitochondria to synthesize ATP is diminished by ethanol consumption. Experiments are designed to pinpoint those ethanol-related lesions in the mitochondrion that limit the rate and/or the extent of ATP synthesis. The above studies will correlate early changes in cardiac energy metabolism and morphological alterations which are related to ethanol consumption. A careful characterization of these early changes related to ethanal consumption should suggest molecular transformations which ultimately lead to the permanent cardiac damage observed in many chronic alcoholics. These studies thus are important in elucidating the pathogenesis of alcohol-induced cardiac disease.