Ischemia impairs oxidative substrate metabolism as well as the mechanical and electrical functions of the myocardium. Previous investigations have shown an accelerated glycolytic flux in ischemic myocardium and have suggested that identification of residual glucose metabolic activity distinguishes hypoperfused, functionally impaired tissue from that which has been irreversibly injured due to antecedent infarction. With positron emission tomography (or PET) and labeled tracers of myocardial perfusion and glucose utilization, it is now possible to noniovasively assess both myocardial blood flow and glucose metabolism in vivo. The purpose of this investigation is to test the hypothesis that quantitative, noninvasive measurements of myocardial blood flow and, more importantly, glucose utilization, made with PET will more accurately reflect tissue viability (and therefore potential for myocardial salvage) than currently used clinical tests (electrocardiogram, analysis of segmental wall motion, thallium scinitgraphy). In Phase I, the applicant will gain experience in canine preparations of myocardial ischemia and infarction and validate tracer kinetic models reparations with the goal of making accurate, noninvasive measurements of myocardial blood flow (rubidium-82, N-13 ammonia) and glucose utilization (F-18 deoxyglucose in vivo with PET. Thus, during this phase the applicant will gain expertise in the basic aspects of PET technology. In Phase II, the tracer kinetic models developed will be validated in human subjects. Quantitative measurements of blood flow and glucose utilization made with PET would then be used to address the following questions: 1) To what extent may blood flow be reduced and yet support myocardial glucose metabolism? 2) Can noninvasive measurements of myocardial glucose utilization and blood flow made with PET predict improvement in segmental function following restoration of blood flow more successfully than the electrocardiogram, thallium scintigraphy, or analysis of wall motion? 3) To what extent can dietary state influence the uptake of glucose in ischemic myocardium? 4) Can quantitative measurements of blood flow and glucose utilization be used to assess the myocardial response to an ischemic insult and predict functional recovery? and 5) can quantitative measurements of blood flow and glucose utilization be used to predict long term prognosis in patients with ischemic heart disease?
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