Cardiomyopathy is a term used to describe a diseased heart muscle resulting in cardiomegaly and congestive heart failure in the absence of coronary artery or congenital heart diease. Congestive cardiomyopathy is one form of this disease which results in a large dilated heart with poor contractile function. Little is known about metabolic function and substrate utilization in humans or animal models of congestive cardiomyopathy. The Syrian golden hamster (strain BIO 14.6) is the most intensively studied animal model of congestive cardiomyopathy. This animal develops an autosomally recessive inherited progressive muscular dystrophy which affects the heart in 100% of the animals. The majority of investigations with this hamster have involved study of the relationships of ionic fluxes to the resultant congestive heart failure. Little emphasis have been placed on the role that derangements in cardiac metabolism play in the early stages of this myopathy. It is known that utilization of long-chain free fatty acids, which are the primary substrate in the normal heart, is significantly decreased in cardiomyopathy. The purpose of this research proposal is to test the hypothesis that the basic defect in congestive cardiomyopathy is a decreased carnitine transport into the myocardial cell resulting in decreased long-chain fatty acid utilization and lower energy production.
The specific aims are to: 1) characterize cardiac metabolism in the Syrian hamster with congestive cardiomyopathy; and 2) test the therapeutic efficacy of exogenous carnitine as a therapeutic agent for this disease in the hamster model.
