METABOLIC ADAPTATIONS TO REPETITIVE MYOCARDIAL ISCHEMIA

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DESCRIPTION: (Adapted from the Investigator's Abstract) Preconditioning induced by repeated brief myocardial ischemia each separated by another brief period of reperfusion protects the myocardium from subsequent ischemia reperfusion injury. One of beneficial consequences of preconditioning is progressive preservation of high energy phosphate compounds which is reflected by the progressively greater attenuation of the increase in interstitial fluid (ISF) purine metabolites. The proposed research will examine the threshold of the attenuated purine metabolite accumulation by addressing two Specific Aims: 1) by determining the minimum time and degree of ischemia necessary to induce attenuated purine metabolite accumulation during subsequent global ischemia and 2) by determining the effect of adenosine kinase or adenosine deaminase inhibition on ISF purine metabolite accumulation and by studying the rate of adenosine formation during preconditioning.