A major aim of the proposed project is to investigate changes in myocardial lipids under ischemic and infarcting conditions, to correlate such changes with other parameters of ischemia on a cellular and subcellular level, and to explain the structural changes of the complex lipids by determining changes in lipid metabolism. Myocardial infarcts will be produced in dogs by coronary artery ligation. Progressive changes with time will be followed over a 72-hr period and gradients of change will be established in each infarcted area. Changes in the molecular structure of complex lipids will be correlated with histological and electron microscopic evidence and with changes in mitochondrial function. Turnover rates of complex lipids will be measured in normal rat myocardium and in isoproterenol induced cardiomyopathy. Short-term effects of anoxia leading to irreversible changes in membrane permeability will be studied in the perfused rat heart. Pathways and mechanisms of phospholipid biosynthesis and degradation will be investigated with homogenates and subcellular preparations of normal and ischemic myocardium. Long-term goals of the proposed research are to understand the sequence of biochemical changes which occur under ischemic conditions, how they are expressed in changes of lipid metabolism, how membrane lipids are affected by these events and how irreversible damage to the myocardium may be prevented or minimized.
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