The long-term goal of the research is to understand the movement of water and solute across the capillary wall in resting and exercising skeletal muscle. The approach is to measure fundamental transport parameters in isolated whole organ muscle preparations perused under controlled cardiovascular conditions with solutions of set composition. The primary purpose of the proposed studies is to test the hypothesis that water crosses the capillary wall of resting muscle mainly through pathways which largely exclude small molecules the size of sucrose and sodium chloride. This hypothesis is a major change from the conventional view that most water flow occurs through pathways large compared to these solutes. The hypothesis is based on recently published values of the osmotic reflection coefficient, sigma d, for sodium chloride and other small solutes. Measured in osmotic transient experiments, the values were dependent on the perfusate flow rate through the muscles. The specific hypothesis being tested is that the flow dependence is caused by 1) a modest increase (less than or equal to 50%) in the total hydraulic conductivity, THC, with flow, and 2) a large increase in the average capillary concentration with flow, as predicted by theory. THC will be determined by measuring the weight changes in a muscle preparation following step in colloid osmotic pressure, an existing method with advantages in this application. The average capillary concentration will be determined by arterial and venous concentrations and assuming an exponential profile, an assumption well supported by theory. The preparation used to date has been the hindlimb. The isolation procedure causes significant trauma to the perfused muscles. To assess the importance of this, studies will be mainly performed in a calf preparation in which the muscles are undamaged. These basic studies will deepen our understanding of important physiological processes which have applications in disorders involving water and solute distribution such shock, inflammation, and edema.
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