The purpose of this project is to investigate the regulation of fatty acid utilization in heart muscle. The isolated perfused rat heart and isolated heart mitochondria will be used for these studies. The perfused heart preparation utilized FFA in the preference to carbohydrate as substrate for energy metabolism. The rate of fatty acid utilization can be varied by raising the concentration of exogenous fatty acid, by increasing cardiac work and by decreasing oxidative metabolism. The mechanisms of these changes in fatty acid utilization will be investigated in the whole tissue by measuring the rates of fatty acid uptake and oxidation and the levels of key metabolic intermediates in the pathways. Earlier studies using this approach have indicated that the rate of the citric acid cycle controls the rate of fatty acid oxidation at physiological concentrations of palmitate and at low cardiac work loads. With increased cardiac work, the cycle was accelerated and oxidation of fatty acyl carnitine limited utilization of fatty acids. The mechanisms of these effects will be investigated in the whole tissue and in isolated mitochondria.