ADRENERGIC LIMITATION OF CORONARY FLOW DURING EXERCISE

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Previous studies under this grant indicate that an alpha-constrictor tone limits myocardial perfusion and as a result imposes a limitation on myocardial contractile function. Because of the potential importance of this adrenergic effect on coronary perfusion and myocardial function during physical exertion in the human, four new studies are proposed. Research studies by others suggest that the alpha-constriction is mediated by circulating catecholamines rather than to neural mechanisms, while pilot studies from this laboratory indicate that neural mechanisms play a large role. Therefore, Study 5 will examine whether the coronary alpha- constrictor tone is mediated primarily humoral or by neural mechanisms. Studies also conflict with regard to the transmural distribution of an alpha-constrictor tone and its physiological importance in modulating myocardial blood flow. Study 6 will examine the transmural nature of he adrenergic constrictor tone and its effect on transmural myocardial function during exercise. Studies by others have shown that during progressive coronary occlusion, there is a reduction in flow leading to a reduction in contractile function long before the coronary dilatory reserve capacity is exhausted. Study 7 will examine whether the alpha-constrictor tone varies with the intensity of exercise, and whether the constrictor tone, as a result of restricting coronary flow also imposes a limitation on maximal cardiac performance at maximal levels of exercise. The specific alpha-receptor subtypes involved will also be examined. Pilot studies indicate that holding flow constant during mild exercise induces a sympathetic vasoconstriction. Therefore, Study 8 will examine whether ischemia during exercise elicits a neural reflex which imposes a coronary alpha-constriction. These important studies will be applicable to the treatment of the human with pre-existing coronary artery disease, especially during exertion.