NMR STUDIES OF CONGESTIVE HEART FAILURE

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DESCRIPTION: In this proposal the investigator outlines a series of further experiments designed to test his hypotheses that hearts in congestive heart failure (CHF) show transmural differences in phosphorus metabolites under high workloads and demonstrate alterations in the catabolism of carbon substrates. Localized and non-localized 31P and 13C NMR techniques will be used to for transmural analysis of function, blood flow, and metabolism in a tachycardiac dog model. 13C NMR experiments, using a variety of 13C- enriched substrates, are designed to elucidate several biochemical questions, including changes in substrate selection and in substrate utilization in the TCA cycle. 31P NMR will be used to monitor intracellular myocardial pH and phosphorus metabolite levels using spatial localization methods to test the hypotheses that CHF alters the myocardium's ability to support mechanical and cellular functions optimally, and that these alterations will be more pronounced in endocardial tissue at high workloads. Saturation transfer methods will also be used to measure flux though the creatine kinase reaction across the ventricular wall. Additional experiments will elucidate the changes which precede the onset of CHF and examine the combined effects of CHF and acute ischemic injury.