The intent of this RCDA application is to provide support for my development as an independent investigator in the area of microcirculation. My emphasis is directed towards the study of transvascular movement of fluid and solutes across capillaries and the interstitial space. In many pathological conditions, there is an imbalance in the partition of fluid and solutes between the vascular and extravascular spaces. Fluid exchange across the microvasculature is partially controlled by the interstitial hydrostatic and oncotic pressures. The interstitial oncotic pressure is determined by the distribution of extravascular plasma proteins in the interstitial gel matrix, composed of collagen and glycosaminoglycans. Thus, my goal is to study the transport and distribution of plasma proteins in the interstitial gel matrix, composed of collagen and glycosaminoglycans. Thus, my goal is to study the transport and distribution of plasma proteins in the interstitium during different types of edema and relate the data to the present concepts on the control of fluid balance in the body. Our preliminary studies indicate that the transport of plasma proteins through the interstitial matrix following saline expansion is different than that following increased venous pressure or increased capillary wall permeability to plasma proteins. I propose to test the hypothesis that plasma proteins are carried from plasma to lymph through free fluid channels following venous congestion or alterations in endothelial permeability, and through the gel matrix following saline expansion or chronic plasmaphoresis. In anesthetized rabbits we will determine the initial equilibration rates for tracer albumin and IgG from plasma to lymph. I will study both skin and skeletal muscle in the rabbit hindpaw. I will compare the equilibration rate for tracer albumin between plasma and lymph tothat between plasma and the interstitial space. I will also test the hypothesis that there is electrostatic exclusion, in addition to steric exclusion, of albumin from portions o the interstitial gel. These results will provide information on the role of the interstitial matrix in tissue fluid balance as well as provide insight into the etiology of edema formation. This project will also form a focus for my research efforts over the next 5 years as I develop my career as a professional physiologist and independent scientist in the field of microcirculation.
