The emphasis in the proposed program is on the elucidation of mechanisms of transport of small solutes from the blood into myocardial cells and on the evaluation of the characterizing transport rates across the capillary wall, via trans- or inter-endothelial cell routes through the interstitium and across the sarcolemma. Previous work has gone a long way in obtaining clear mathematical descriptions of intravascular transport; the proposed work puts a new emphasis on the mechanisms of capillary transport, particularly for fatty acids and substances which traverse the endothelial cells via facilitated or passive mechanisms. The work includes a sequence of studies designed to obtain more precise evaluations of transport of hydrophilic solutes across the capillary wall for a variety of sizes of probing molecules and to "finally" resolve the disparities in estimates of capillary permeability by osmotic and tracer transient techniques. The multiple indicator dilution technique will be used to evaluate the unidirectional transsarcolemmal fluxes of glucoses and fatty acids. External detection approaches will be developed to refine the estimates of parameters. The program should produce and evaluate new techniques for estimating fluxes across cell walls in intact organs and provide data on specific solutes in the myocardium of dogs and rabbits. Data on metabolism obtained by tissue sampling techniques will be used in evaluating the ability to assess intracellular reactions from data on intact organs. Our goal is to demonstrate that in vivo organ metabolism can be explored by outflow or external detection.