The long-term objective of this proposal is to observe the development of a cardiomyopathy in the cat heart as it occurs secondarily to the induction of an experimental diabetic state. A second objective is to determine whether or not the diabetic heart is more susceptible to an ischemic insult, and elucidate possible mechanisms involved in the phenomena of diabetic cardiomyopathy and the role of insulin therapy in this pathological state. These objectives will be accomplished by the following specific aims: 1) to characterize mydocardial function and compliance of hearts from normal and streptozotocin-induced diabetes cats by utilizing an isolated heart preparation perfused with blood from a normal or diabetic cat; 2) to determine the effect of global ischemic arrest on the isolated blood perfused diabetic cat heart; 3) to determine the effects of experimental diabetes on myocardial enzymes, energy substrates and subcellular organelle function during normal perfusion and after global ischemic arrest; and 4) to assess the effects of insulin therapy on the prevention and reversal of the diabetic cardiomyopathy and biochemical correlates. This study, as outlined, should allow us to gain a better understanding of the relationship between the diabetic state and developing cardiomyopathy and provide information for the treatment of ischemia in the diabetic heart which occurs at a higher frequency in diabetics. This study will also provide evidence as to the validity of the experimental diabetic cat as a model of human diabetes mellitus.
