The ultimate goal of this work is to understand the limits to and control of tissue oxygenation. Current views of the local control process are inadequate to account for certain integrative phenomena and for the capillary oxygen content. We will explore this problem in two lines of experimental investigation. First, structure- function relations in small arteries, arterioles and capillaries will be assessed in relation to regulation of total blood flow, heterogeneity of blood flow and intracapillary oxygen content. These experiments will be executed using techniques including: three dimensional reconstruction of the patterns of fluorescent red cells, in situ microvessel perfusion with artificial blood, and servo-null measurement of intravascular pressure, 3-dimensional reconstructions of the red cell flow patterns will be used in the formulation of a modular mathematical model of the red cell flow distribution in the microvascular tree. The importance of endothelial cell surface structures as determinants of capillary tube hematocrit will be determined using selective enzymatic attack on the endothelial cell surface glycoproteins. This work will be complemented by thin and thick section electron microscopy and 3- dimensional reconstructions of the vessel wall. The second line of investigation will employ microperfusion and microiontophoresis to induce and study propagated and flow-dependent vasomotor responses. These data will be employed in a description of the nature of longitudinal communication along the vascular axis. We will utilize selective damage and intracellular marking with lucifer yellow to ascertain the cell types responsible for the propagated responses. Enzymatic treatment will be used to explore the cellular basis for flow-dependent vasodilation. The experimental findings should provide a quantitative definition of the factors that limit tissue oxygenation. In addition, fundamental new information should be derived concerning the rules for longitudinal integration of vascular function.
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