The proposed research will use the principles of tracer and competitive enzyme kinetics and positron computed tomography (PCT) imaging techniques to define the myocarial kinetics of radioactive labeled yet physiologically active tracers of metabolism and their relationship to specific metabolic processes such as exogenous glucose and fatty acid utilization, myocardial oxygen consumption and blood flow. Tracer kinetic models will be adopted or developed to mathematically describe these kinetics, (i.e., the transmembranous exchange and turnover rates in terms of compartments or functional units that correspond to a specific physiologic or metablic step) and used to formulate operational equations, through which in vivo but non-traumatic quantification of regional myocardial metabolism, blood flow and oxygen consumption will become possible with PCT. The work will be performed largely in acute and chronic dog experiments which also will be used to test and validate these models and the accuracy of the anticipated regional measurements of myocardial metabolism and blood flow. These measurements will be correlated with regional myocardial mechanical function. Hence, oxygen and substrate delivery as well as mechanical function can be related to regional myocardial metabolism. The anticipated accomplishments should allow, for the first time, accurate in vivo measurements of regional myocardial metabolism in man. Such capability should provide in new insights into the physiology of the normal and abnormal heart, allow better delineation of the location and extent of cardiac disease, evaluation of the effects of therapy, and lastly, permit detection and characterization of cardiac disease at the biochemical level perhaps at a pre-clinical stage.
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