The objectives of the proposed research are: 1) to explore the usefulness of the cardiac microdialysis technique for the sampling of intramyocardial interstitial fluid (ISF) and measurement of regional coronary blood flow (CBF); and 2) to use the cardiac microdialysis technique to study the cardiac effects of adenosine. In the proposed experiments, cardiac microdialysis, used to determine ISF levels of adenosine, inosine, hypoxanthine, xanthine, uric acid, and lactate, would be utilized in conjunction with standard techniques for the measurement of regional ventricular function and metabolism to perform four series of experiments. Series 1 would assess the validity, applicability, and limitations of the cardiac microdialysis technique. The experiments of Series 2 would take advantage of the capability of the cardiac microdialysis technique to deliver pharmacological agents locally to the tissue surrounding the microdialysis probe, using this approach to study adenosine metabolism and action. In Series 3, cardiac microdialysis would be used to investigate changes in regional ISF purine metabolites and lactate would be correlated to changes in local CBF and regional ventricular function during hypoxia, inotropic stimulation, and graded reductions in coronary artery perfusion pressure. In Series 4, cardiac microdialysis would be used to investigate myocardial ischemia, focusing on interventions which alter endogenous adenosine levels during ischemia.
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