The primary purpose of this study is to determine the contribution of red blood cell aggregation to the function of the venous microcirculation. Aggregation greatly increases blood viscosity at low shear rates in rotational viscometers. This finding has led to the suggestion that aggregation contributes significantly to vascular resistance, especially at low flow rates. However, studies of total vascular resistance in isolated organs during perfusion with blood of elevated or reduced aggregability have yielded inconsistent results and failed to confirm an effect of aggregation. Aggregation has also been proposed as the primary cause of the inverse relation between blood flow and venous vascular resistance seen in skeletal muscle. However, studies have shown that aggregation does not increase apparent blood viscosity at low flow rates in small glass tubes of the size of venules. Current experimental studies in the investigator's laboratory provide a new perspective on this question. Using the lateral gastrocnemius muscle preparation of the cat, which allows continuous determination of postcapillary resistance, the applicants have obtained evidence that red cell aggregation may be responsible for at least 50% of the total venous vascular resistance in resting skeletal muscle. Moreover, it appears that the inverse relation between flow and venous resistance in this muscle is largely, if not entirely, due to red cell aggregation. This effect appears to be maximal with normal blood; if aggregability is either increased or decreased from normal levels, the inverse relationship is weakened, or, in some cases, completely lost. In this project the investigators propose to determine more precisely the quantitative contribution of aggregation to venous vascular resistance over a range of flows and varying degrees of red cell aggregability. They will also examine the possible contribution of changes in vascular geometry to the change in venous resistance. Using microcirculatory preparations, the applicant will seek to identify the key factors responsible for the effects of aggregation on venous vascular resistance and to quantify changes in vessel geometry. Theoretical studies will model blood flow in venular segments and at venular bifurcations, and will utilize experimental findings to develop a realistic model of aggregation and its effects on hydrodynamic resistance in the venular circulation. These studies should improve our understanding of the hemodynamics of the venous microcirculation and document a physiological role for red cell aggregation for the first time. The studies may also aid in understanding the functional consequences of increased red cell aggregability found in certain clinical disorders.
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