The proposed program is focused on mechanisms of transport of small solutes from the blood into the myocardium and in particular on the characterization of transport across the capillary wall, via trans- and inter-endothelial cell routes. Previous work has gone a long way in obtaining clear mathematical descriptions of intravascular and transcapillary transport. The new emphasis is on the mechanisms of transport, particularly for fatty acids and adenosine into or across endothelial cells via facilitated or passive mechanisms. The multiple indicator dilution technique will be used to evaluate the unidirectional plasmalemmal fluxes of adenosine and fatty acids. Specific experiments will be done to test the hypothesis that the membrane transporters for adenosine and inosine can behave as facilitating countertransporters, that is, show augmentation of cis to trans flux by raising the trans-concentrations. The program should result in proven new techniques for estimating fluxes across endothelial cell walls in intact organs and provide data on specific solutes in the myocardium of dogs and rabbits.
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