Cardiovascular control is effected by a combination of neural, humoral and local (intrinsic) mechanisms. The immediate goal of this study is to develop a quantitative understanding of local blood flow control at the level of the microcirculation, the cardiovascular supply capacity must balance tissue metabolism, particularly in relation to oxygen supply and demand. Specifically, this study aims to examine quantitatively the control of red cell volume flow through capillaries: 1. by seeking to determine how the number of erythrocytes reaching a capillary network is regulated, and 2. by examining the significance for oxygen delivery of variations in transit time of red blood cells across capillary networks. These studies are made possible by a new technique which I have developed, and which enables, for the first time, direct measurement of key microcirculatory variables. These are red cell flux (in vessels larger than capillaries), red cell transit time and blood flow path across capillary networks. The technique also enables simple and direct measurement of microvessel hematocrit. The study will contribute substantially to understanding local control of blood flow and tissue oxygenation. In particular, by determining the influence of microvascular architecture on transit time and blood flow path changes, this study will clarify blood flow responses in tissues with complex microvascular architecture (e.g., brain) on where peripheral vascular pathology is characterized by deviations in network geometry. Examples are the extreme tortuosity of the conjunctival circulation in diabetes mellitus or the microvascular rarefaction associated with hypertension. By evaluating the role of red cell volume flow in oxygen delivery in association with progressive changes in microvascular geometry, these studies will also contribute significantly to our understanding of the processes underlying adaptive changes in blood flow control, for example, those initiated by exercise training, or seen in chronic anemia.
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