Piantadosi C A, Sylvia A L, Jöbsis F F
J Clin Invest. 1983 Oct;72(4):1224-33. doi: 10.1172/JCI111078.
The sensitivity of the brain to cyanide-induced histotoxic hypoxia and the protective effects of known cyanide antagonists, have been assessed in vivo by reflectance spectrophotometry. Cyanide-related changes in cytochrome a,a3 (cytochrome c oxidase) oxidation-reduction (redox) state, tissue hemoglobin saturation, and local blood volume were continuously monitored in cerebral cortex of rats. Noncumulative, dose-dependent inhibition of the in situ mitochondrial respiratory chain was evaluated directly by measuring increases in reduction levels of the terminal oxidase. These transient cytochrome a,a3 reductions were accompanied by increases in regional cerebral hemoglobin saturation and blood volume. Cytochrome redox responses were not altered either in magnitude or kinetics by hyperoxia; however, the cyanide-cytochrome dose-response curve was greatly shifted to the right by pretreatment with sodium nitrite, and the recovery rate of cytochrome a,a3 from cyanide-induced reduction was enhanced fourfold by pretreatment with sodium thiosulfate.
通过反射分光光度法在体内评估了大脑对氰化物诱导的组织中毒性缺氧的敏感性以及已知氰化物拮抗剂的保护作用。在大鼠大脑皮层中持续监测细胞色素a,a3（细胞色素c氧化酶）氧化还原状态、组织血红蛋白饱和度和局部血容量与氰化物相关的变化。通过测量末端氧化酶还原水平的增加直接评估原位线粒体呼吸链的非累积性、剂量依赖性抑制。这些细胞色素a,a3的短暂还原伴随着局部脑血红蛋白饱和度和血容量的增加。高氧对细胞色素氧化还原反应的幅度或动力学均无改变；然而，亚硝酸钠预处理可使氰化物-细胞色素剂量反应曲线大幅右移，硫代硫酸钠预处理可使细胞色素a,a3从氰化物诱导的还原中恢复的速率提高四倍。
