"Analysis of oxygen releasing behavior of hemoglobin-vesicles (nano-particles) and the mechanism of oxygenation of ischemic tissue."

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The purpose of this project was to clarify the mechanism and optimization of oxygenation of ischemic tissues by a suspension of hemoglobin-vesicles (HbV). One advantage of HbV is that O_2 affinity (P_<50>) of Hb can be easily regulated by manipulating the allosteric effectors coencapsulated in HbV. One concept is that the low P_<50> HbV would retain O_2 in the normal tissue while unloading O_2 to a targeted hypoxic tissue. HbV (P_<50> =9 mmHg) enhanced oxygenation of an ischemic part of hamster dorsal skin flap where tissue O_2 tension was significantly reduced. Injection of HbV increased the plasma viscosity, thus enhance the vasorelaxation and the resulting recovery of blood flow and oxygen delivery via collateral artery. In another experiment, low P_<50> HbV showed slower O_2 unloading in the occluded arterioles in comparison with normal P_<50> HbV. The contribution of the low P_<50> HbV as the source of O_2 supply exceeds that of RBC even with a small dosage of HbV, indicating the possible utilization of HbV for O_2 therapeutics. These findings indicates that manipulation of the physicochemical properties of HbV enables possible use of tailor-made artificial oxygen carriers for many clinical indications.