The studies proposed in this application are designed to determine the mechanism of alteration in myocardial function and metabolism in diabetic animals. Maximum cardiac contractility is depressed in hearts isolated from diabetic animals and perfused in vitro. The mechanism of this effect may relate to the known decrease in thyroxine levels in diabetic animals and to the known effect of thyroxine deficiency on depression of myocardial myosin ATPase and contractility. Myocardial synthesis of coenzyme A from pantothenic acid is increased in diabetic animals. The mechanism of this effect will be studied in broken cell preparation and in isolated perfused hearts in order to determine the step(s) in the pathway that control synthesis and the factors that regulate this step.