A quantitative framework for the design of acellular hemoglobins as blood substitutes: Implications of dynamic flow conditions

The delivery of oxygen to tissue by cell-firee carriers eliminates intraluminal barriers associated with red blood cells. This is important in arterioles, since arteriolar tone controls capillary perfusion. We describe a mathematical model for O-2 transport by hemoglobin solutions and red blood cells flowing through arteriolar-sized tubes to optimize values of p50, Hill number, hemoglobin molecular diffusivity and concentration. Oxygen release is evaluated by including an extra-luminal resistance term to reflect tissue oxygen consumption. For low consumption (i.e., high resistance to O-2 release) a hemoglobin solution with p50 = 15 mmHg, n = 1, D-HBO2 = 3 x 10(-7) cm(2)/s delivers O-2 at a rate similar to that of red blood cells. For high consumption, the p50 must be decreased to 5 mmHg. The model predicts that regardless of size, hemoglobin solutions with higher p50 will present excess O-2 to arteriolar walls. Oversupply of O-2 to arteriolar walls may cause constriction and paradoxically reduced capillary perfusion. (C) 2007 Elsevier B.V. All rights reserved.