OXYGEN AFFINITY AND OXYGEN TRANSPORT IN STRIATED MUSCLE

该项目的目标是评估补偿性 氧运输的改变发生在 横纹肌微循环水平的变化， 通过增加或减少亲和力诱导的氧输送 红细胞血红蛋白中的氧。 实验将 在金的颊囊牵开肌上进行手术， 仓鼠。 氧亲和力将由以下位置决定： 氧合血红蛋白解离曲线通过测定 标准P50（氧分压（P02），红细胞 血红蛋白在pH 7.4时饱和50%，碱过量= 0.37 摄氏度）。 氧亲和力的变化将通过以下方式实现： 要么是长期短期服用氰酸钠 （左移）或邻碘苯甲酸钠（右移）或急性 用已被移植的供体红细胞进行输血 在体外用氰酸钠（左移）或肌醇处理 六磷酸盐（右移）。 氧气的变化 亲和力将通过评价几何（管腔）特性来评估 直径;毛细血管密度）、血液动力学（红细胞 流速;大血管血红蛋白浓度;毛细血管线型 密度）、氧合（氧饱和度（SO2））和氧 交换（纵向SO2梯度）参数， （小动脉和小静脉）和小（毛细血管）微血管。 的 大型船舶的数据将进行在线分析， 毛细管将从录像带中离线分析， 最先进的方法 从动物身上获得的数据 与改变的氧亲和力将比较类似的数据 从适当年龄匹配的假处理对照组中获得 动物 初步研究将在常氧条件下进行， 休息条件。 我们随后将评估 氧亲和力的改变对肌肉氧合的影响 存在改变的氧气供应（改变的吸入P02）， 增加的氧气需求（肌肉收缩）和组合 氧气供应减少而氧气需求增加。 这些研究将提供宝贵的信息， 为横纹肌提供充足的氧气 肌肉和洞察其在其他组织中的重要性， 适当的氧气供应对动物的 生存 此外，这些研究将提供有用的 关于同时发生的临床 外周氧利用受损的观察结果 和血红蛋白氧亲和力改变。

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.