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-free 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 O2 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 O2 release) a hemoglobin solution with p50 = 15 mmHg, n = 1, DHBO2 = 3 × 10− 7 cm2/s delivers O2 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 O2 to arteriolar walls. Oversupply of O2 to arteriolar walls may cause constriction and paradoxically reduced capillary perfusion.