OXYGEN AFFINITY AND OXYGEN TRANSPORT IN STRIATED MUSCLE

本项目的目标是评估补偿 氧运输的变化发生在 横纹肌微循环水平的变化 通过增加或降低亲和力而引起的氧输送 从红血球血红蛋白中提取氧气。实验将是 在金色的面颊袋拉肌上做手术 仓鼠。氧亲和力将由以下位置决定 氧合血红蛋白解离曲线的测定 标准P50(血氧分压(P02) 在pH 7.4时，血红蛋白是50%饱和的，碱过量=0，37 摄氏度)。氧亲和力的变化将通过以下方式实现 无论是长期短期服用氰化钠 (左移)或邻碘苯甲酸钠(右移)或急性 与供者红细胞交换输血，这些红细胞已经 体外用氰酸钠(左移)或肌醇处理 六磷酸盐(右移)。氧气变化的影响 将通过评估几何形状(流明)来评估亲和力 直径、毛细血管密度)、血流动力学(红细胞 流速；大血管血红蛋白浓度；毛细血管直线型 密度)、氧合(血氧饱和度(S02))和氧气 交换(纵向S02梯度)参数在两个大的 (小动脉和小静脉)和小(毛细血管)微血管。这个 大型船舶的数据将在线分析，而大型船舶的数据将 毛细血管将从录像带中脱机分析，使用 最先进的方法论。从动物身上获得的数据 将氧亲和力改变的数据与类似的数据进行比较 取自适当年龄匹配的假治疗对照组 动物。初步研究将在常氧条件下进行， 休息条件。我们随后会评估 氧亲和力对大鼠肌肉氧合作用的影响 存在改变的氧气供应(改变的灵感P02)， 氧气需求增加(肌肉收缩)和一种组合 氧气供应减少而需氧量增加。 这些研究将提供有价值的信息，说明 为纹状体提供充足氧气的氧亲和力 肌肉和对其在其他组织中的重要性的洞察 适当的氧气供应对动物的 生死存亡。此外，这些研究应该提供有用的 关于重合临床的关系的信息 外周血氧利用障碍的观察 并改变了血红蛋白对氧的亲和力。

The goal of this project is to evaluate the compensatory alterations in oxygen transport which occur at the microcirculatory level in striated muscle following changes in oxygen delivery induced by increasing or decreasing the affinity of the red blood cell hemoglobin for oxygen. Experiments will be performed on the cheek pouch retractor muscle of the golden hamster. Oxygen affinity will be determined by the position of the oxyhemoglobin dissociation curve assessed by determining a standard P50 (oxygen tension (P02) at which red blood cell hemoglobin is 50% saturated at pH 7.4, Base Excess = 0, 37 degrees C). Changes in oxygen affinity will be accomplished by either the chronic, short term administration of sodium cyanate (left-shift) or ortho-iodosodium benzoate (right-shift) or acute exchange transfusion with donor red blood cells which have been treated in vitro with sodium cyanate (left-shift) or inositol hexaphosphate (right-shift). The impact of alterations in oxygen affinity will be assessed by evaluating geometric (luminal diameter; capillary density), hemodynamic (red blood cell velocity; large vessel hemoglobin concentration; capillary lineal density), oxygenation (oxygen saturation (S02)) and oxygen exchange (longitudinal S02 gradient) parameters in both large (arterioles and venules) and small (capillaries) microvessels. The data on the large vessels will be analyzed on-line while that for the capillaries will be analyzed off-line from video tapes using state-of-the-art methodologies. The data obtained from animals with altered oxygen affinity will be compared with similar data obtained from appropriate age-matched, sham-treated control animals. The initial studies will be undertaken under normoxic, resting conditions. We will subsequently assess the impact of alterations of oxygen affinity on muscle oxygenation in the presence of an altered oxygen supply (altered inspired P02), increased oxygen demand (muscle contraction) and a combination of a decreased oxygen supply with an increased oxygen demand. These studies will provide valuable information on the importance of oxygen affinity for the adequate supply of oxygen to striated muscle and insights into its importance in other tissues for which the appropriate supply of oxygen is crucial to the animal's survival. In addition, these studies should provide useful information on the relationship between the coincident clinical observations of an impairment of peripheral oxygen utilization and altered hemoglobin oxygen affinity.