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

本研究的目的是阐明血红蛋白囊泡（HbV）悬浮液对缺血组织氧合的机制和优化。HbV的一个优点是<50>可以通过操纵HbV中的变构效应物来调节Hb的O_2亲和力（P_）。一种观点认为，低P_<50>HbV会将O_2保留在正常组织中，而将O_2卸载到靶向缺氧组织。HbV（P = <50>9 mmHg）可使组织氧分压明显降低的仓鼠背部皮瓣缺血部位氧合增强。注射HbV可增加血浆粘度，从而增强血管舒张，并由此恢复侧支动脉的血流量和氧输送。在另一项实验中，<50>与正常P_ HbV相比，低P_ HbV显示闭塞小动脉中O_2卸载较慢<50>。低P_<50>HbV作为O_2供应源的贡献甚至在小剂量HbV的情况下也超过RBC，表明HbV可能用于O_2治疗。这些研究结果表明，操纵HbV的理化性质使定制的人工氧载体可能用于许多临床适应症。

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.