HYPOTHERMIC CONDITIONS AFFECT O2-CARRYING CAPACITY OF CROSSLINKED HEMOGLOBINS

鉴于HBOCs在器官灌注中的潜在应用， 心脏停搏液在大手术期间，或保存在低 移植前的温度，我们检查了温度依赖性 氧平衡曲线（OECs）在15-37摄氏度， 人和牛交联血红蛋白的数量。 OECs对于这些 血红蛋白在装有 恒温电池 在37 ℃时，修饰血红蛋白的OEC为 与未修饰的血红蛋白相比右移。 降低 然而，温度导致对氧的亲和力增加。 它 将OEC移到左边。 然而，牛血红蛋白交联在 β-β亚基表现出显著不同， 在非常低的温度下氧化。 这是一个新的情况 开发了与吡哆交联的改性人血红蛋白 四磷酸衍生物。 这使我们相信，不仅 改性的部位，也是化学改性的性质 在确定构象的程度中起着至关重要的作用 在装载和卸载氧气时对血红蛋白施加约束。 这将最终决定其作为灌注液的有用性， 低温条件下。 与这些结合的动力学表征 血红蛋白目前正在使用快速反应技术， 将血红蛋白的平衡和动力学表现联系起来 在低温条件下发挥作用。 这项工作在第四届国际血液研讨会上发表 替代品（1991年8月19日至23日，加拿大。

In view of the potential application of HBOCs in perfusion of organs for cardioplegia during major surgery, or for preservation at low temperatures before transplant, we examined temperature dependence profiles of oxygen equilibrium curves (OECs) at 15-37 degree c for a number of human and bovine crosslinked hemoglobins. OECs for these hemoglobins were carried out on the HEMOX-ANALYZER fitted with a thermostated cell. OECs for modified hemoglobins at 37 degrees c were right shifted as compared to unmodified hemoglobin. Lowering the temperature however, resulted in increased affinity towards oxygen. It shifted OEC to the left. However bovine hemoglobin crosslinked at the beta-beta subunits exhibited significantly different and more favorable oxygenation at very low temperature. Such is the case with a newly developed modified human hemoglobin crosslinked with a pyridoxyl tetraphosphate derivative. This led us to believe that not only the site of modification, but also the nature of the chemical modification plays a crucial role in determining the degree of conformational constrains placed upon the hemoglobin when loading and unloading oxygen. This will ultimately determine its usefulness as a perfusate under hypothermic conditions. Kinetic characterization of binding to these hemoglobins is now underway using fast reaction techniques in an attempt to relate both equilibrium and kinetic manifestations of hemoglobin function under hypothermic conditions. This work was presented at the IV International Symposium on Blood Substitutes (August 19-23, 1991, Canada.