Exercise training has been reported to be beneficial in preventing and/or treating coronary heart disease. However, the primary underlying mechanisms and the relative importance of training induced changes in the coronary vascular bed are not clear at this time. The major goal of the research outlined in this proposal is to provide a better understanding of the effects of exercise training on basic coronary function. Since the purpose of the coronary circulation is to transport nutrients and oxygen to the myocardial cells and to transport metabolites away from these cells, this grant focuses on the effects of training on coronary transport capacity. During the first year of this grant it was found that coronary transport capacity can be quantitated by measuring coronary blood flow reserve capacity and coronary capillary diffusion capacity. It was then found that exercise trained dogs have a large increase in coronary transport reserve in that blood flow and capillary diffusion capacities are both increased. The research outlined in this proposal will attain 5 specific aims that will determine the mechanisms responsible for and functional significance of this change: 1. Determine the mechanisms responsible for the exercise training induced increase in coronary transport reserve. 2. Determine the role of the sympathetic nervous system in the exercise training induced increase in coronary transport reserve. 3. Determine how the exercise training induced changes in the coronary vascular bed influence capillary transport during acute myocardial ischemia. 4. Determine the effects of exercise training on coronary transport reserve in minature swine. 5. Determine how the training induced increase in coronary transport reserve influences coronary transcapillary exchange and exchange capacity in conscious dogs. Transcapillary exchange will be measured with the multiple indicator diffusion technique. Coronary blood flow will be measured in conscious and anesthetized dogs with electromagnetic flow meters. Regional coronary blood flow and gross blood flow heterogeneity will be determined with the radiolabeled microsphere technique.
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