(47g) Engineering Polymerized Hemoglobins for Use In Transfusion Medicine

Universal O₂-carrying solutions that can replace the O₂ storage and transport functions of red blood cells will greatly improve clinical outcomes both for trauma victims and for patients undergoing high-blood-loss surgical procedures. These O₂ carriers also will prevent the many serious complications associated with blood transfusions. My talk will address a simple approach for designing hemoglobin-based O₂ carriers (HBOCs). Our design strategy is based on the observation that transfusion of hemoglobin results in vasoconstriction at the microcirculatory level and the development of systemic hypertension. The root cause of this effect stems from the ability of hemoglobin to extravasate through pores in the wall of blood vessels and scavenge nitric oxide (NO) from the surrounding vasculature. This in turn leads to blood vessel constriction and results in the observed hypertensive effect. Therefore, our design strategy will focus on increasing the size of HBOCs so that these molecules are unable to traverse across the wall of blood vessels. In this talk, I will discuss the design, biophysical properties and in vivo response of polymerized hemoglobins. This work is significant in that it will lead to the development of novel O₂ carriers that are safe and efficacious for therapeutic use.