The proposed research is to determine the rate-limiting steps in myocardial adenine nucleotide synthesis by ascertaining the transport and metabolism of nucleosides in isolated myocardial cells. Specifically, these studies will utilize intact hearts, and isolated heart myocytes and endothelial cells to measure nucleoside transport, incorporation, and 5'nucleotidase activity. These studies are novel because a full picture of energy production and nucleoside transport cannot be obtained with intact tissues. The studies also will address the questions of how nucleosides leave cells, how their loss can be prevented during ischemia, and how nucleotide resynthesis can be enhanced following ischemia. It is thought that by understanding these processes and through use of specific interventions, the hypothesis that myocardial mechanical function is dependent on intracellular nucleotides can be tested. Completion of the proposed studies will help achieve the long term goals of development of interventions to protect ischemic tissue and enhance recovery of normal function in perfused ischemic tissue.
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