The overall objective of the proposed research is to gain insight into the significance of the endothelial-cell glycocalyx in terms of its influence on the resistance to blood flow in the microcirculation as well as its rheological implications in red-cell flux. Understanding the functional role of the glycocalyx is essential to determining vascular resistance and oxygen delivery under physiologic and pathologic conditions. The proposed research is specifically aimed at (1) characterizing the rheology of the blood-capillary system through mathematical modeling in order to establish theoretical predictions of physiologically-relevant quantities including apparent viscosity and tube hematocrit, and (2) designing and conducting experiments which directly measure flow quantities in vivo that can be predicted by the theory. The glycocalyx will be modeled as a porous deformable wall layer consisting of a biphasic mixture of an elastic solid and a viscous fluid. Initially, the red cell will be modeled as a rigid pellet capable of invading the glycocalyx. Subsequently, a more realistic model will be developed which includes tightly-fitting deformable cells. Lubrication theory will be used to model the plasma in the gap between the red cell and the glycocalyx. For each model, the fluid-structure interactions which arise between these components will be characterized by a boundary-value problem consisting of a system of differential equations and boundary conditions. Using a combination of analytic and numerical techniques, solutions for the pressure, velocity, and deformation fields will be obtained which correspond to a pressure driven flow in the tube. From these solutions. rheological quantities such as apparent viscosity and tube hematocrit will be computed for both models. Furthermore, using intravital microscopy, in vivo velocities of fluorescently-labeled beads will be measured before and after treatment to remove the glycocalyx. Results of these experiments will test the validity of the mathematical models which are aimed at gaining new understanding of the endothelial- cell glycocalyx.
