HEMOGLOBIN BASED OXYGEN CARRIERS

对人和牛的血红蛋白进行研究，以获得 可用于医疗保健服务的氧气载体 程序。必须克服三个主要困难：短期 血管内滞留时间和高氧亲和力 无细胞条件下的血红蛋白及其血管毒性 存在于溶血物中。牛血红蛋白将特别 对其溶血物进行了调查。牛血红蛋白将是 特别是对其独特的功能特性进行了研究 即它的氧亲和力对阴离子和 对聚磷酸盐相对不敏感。在牛血红蛋白中 在Beta1位有一种蛋氨酸，它取代了 人血红蛋白中的Val-His二肽位于β1-Beta2位置。 这可能是不同的功能态度的原因。 人和牛的血红蛋白。反应牛脱氧血红蛋白 使用富马酸地阿司匹林，可以获得氧气载体 在pH 7.4时，P50接近60毫米汞柱。有一个分子内的 这种化合物的Beta亚基之间的交联键，而 同样的反应会在α亚基之间产生交联键 人类血红蛋白。就像已经注意到的人类溶血物一样， 牛的溶血物抑制了由 兔主动脉环内皮源性松弛因子。他们 不要抑制β受体。 该项目的具体目标是 1)阐明牛血红蛋白的特殊相互作用 与单价和多价阴离子，探索可能的作用 甲硫氨酸在这些现象中处于贝塔1。 2)阐明血红蛋白的结构与功能关系 其四聚体结构已被分子内稳定 交联剂。 3)温和剂延长血红蛋白保留时间 聚合，并通过改变其流体动力学体积。 4)阐明血管毒性的药理来源。 一种血红蛋白溶液。

Human and bovine hemoglobins are investigated for obtaining oxygen carriers which could be used in health care delivery procedures. Three main difficulties must be overcome: the short intravascular retention time and the high oxygen affinity of hemaglobin, in cell-free conditions and the vascular toxicity present in hemolysates. Bovine hemoglobin will be especially investigated for its hemolysates. Bovine hemoglobin will be especially investigated for its peculiar functional characteristics namely the strong sensitivity of its oxygen affinity to anions and the relative insensitivity to polyphosphates. In bovine hemoglobin there is a methionine in position beta1, which substitutes for the Val-His dipeptide in position beta1-beta2 in human hemoglobin. This may be responsible for the different functional attitudes of human and bovine hemoglobins. Reacting bovine deoxyhemoglobin with fumaryl diaspirin it is possible to obtain an oxygen carrier with P50 near 60 mmHg at pH 7.4. There is an intramolecular crosslink between the beta subunits of this compound, while the same reaction produces a crosslink between the alpha subunits in human hemoglobin. As already noticed for human hemolysates, bovine hemolysates inhibit the relaxation produced by endothelium derived relaxing factor in rings of rabbit aorta. They do not inhibit the beta receptor. Specific goals of the project are 1) To elucidate the peculiar interaction of bovine hemoglobin with mono and polyvalent anions, exploring the possible role of the methionine at beta1 in these phenomena. 2) To elucidate the structure function relationship in hemoglobins whose tetrameric structure has been stabilized by intramolecular crosslinks. 3) To prolong the retention time of hemoglobins by mild polymerization and by modifying their hydrodynamic volume. 4) To clarify the pharmacological origin of the vascular toxicity of hemoglobin solutions.