Julia C. Arciero Ph.D. Candidate Applied Mathematics-GIDP Experimental Biology Washington, DC April 28 - May 2, 2007

ABSTRACT
The fundamental role of the circulatory system is to adequately deliver blood to all parts of the body. The demand for oxygen at any point in tissue varies with metabolic activity, growth, and response to various stimuli. The body’s adequate response to this oxygen demand suggests that the body is able to transfer information between a tissue region and the blood vessels that supply the tissue region. To model this process, we investigate possible mechanisms by which blood flow is regulated in response to increased oxygen demand.

Experimental evidence has shown that red blood cells (RBCs) can sense tissue oxygen levels. Upon sensing low oxygen levels, RBCs release an increased amount of ATP that invokes a signal to travel upstream and causes the resistance vessels (arterioles) to dilate so that more blood is sent to the region of demand. These experimental observations suggest that this oxygen sensing mechanism, known as the conducted response, may play an important role in blood flow regulation. To analyze this mechanism, we have developed a theoretical model that simulates the variation of oxygen and ATP levels along a pathway of seven representative segments (artery, large arteriole, small arteriole, capillary, small venule, large venule, and vein). In a representative segment model, multiple segments of a given size and vessel type are grouped together and assumed to be connected in parallel. Each grouping therefore includes vessels of a range of diameters. We include an expression for the conducted response in our model by integrating the ATP concentration along the vascular pathway, taking into account exponential decay of the signal in the upstream direction. Our model predicts that the amount of ATP released increases with increasing consumption rate and with decreasing flow. The extent to which arterioles constrict or dilate depends on the conducted metabolic signal as well as on local wall shear stress and wall tension. The model predicts that combining the responses to these three factors can account for a nearly 10-fold increase in perfusion in response to a 20-fold increase in oxygen demand. Excluding myogenic and shear dependent responses from the model does not greatly alter the perfusion attained at high oxygen demand.