Lee P A, Sylvia A L, Piantadosi C A
Department of Physiology, Duke University Medical Center, Durham, North Carolina 27710.
Toxicol Appl Pharmacol. 1988 Jun 15;94(1):34-44. doi: 10.1016/0041-008x(88)90334-1.
Cyanide-induced cytotoxicity is primarily a result of inhibition of O2 uptake by the terminal enzyme of the mitochondrial respiratory chain, cytochrome-c oxidase (cytochrome aa3). The oxidase in the brain is highly vulnerable to cyanide cytotoxicity, but few studies have evaluated the effects of cyanide on cerebral oxygen metabolism. In the present study, we measured oxidation-reduction responses of cerebrocortical cytochrome aa3 to cyanide and related changes in cerebral blood flow (CBF) and O2 metabolism (CMRO2). Accurate measurement of cytochrome aa3 redox state in vivo by reflectance spectrophotometry was accomplished by using fluorocarbon-circulated rats to eliminate spectral interference from hemoglobin. The data indicate that constant intravenous infusions of cyanide caused rapid, progressive reduction responses by cerebrocortical cytochrome aa3 concomitant with increases in CBF of up to 200%. However, CMRO2 was maintained near normal until cerebral O2 delivery began to fall. These cerebral oxidative responses to cyanide may be explained either by redistribution of intracellular O2 supply to mitochondria respiring in an O2-dependent manner or by branching effects within brain mitochondria in vivo.
氰化物诱导的细胞毒性主要是线粒体呼吸链末端酶细胞色素c氧化酶（细胞色素aa3）抑制氧气摄取的结果。大脑中的氧化酶极易受到氰化物细胞毒性的影响，但很少有研究评估氰化物对脑氧代谢的影响。在本研究中，我们测量了大脑皮质细胞色素aa3对氰化物的氧化还原反应以及脑血流量（CBF）和氧代谢（CMRO2）的相关变化。通过使用氟碳循环大鼠消除血红蛋白的光谱干扰，采用反射分光光度法在体内准确测量细胞色素aa3的氧化还原状态。数据表明，持续静脉输注氰化物会导致大脑皮质细胞色素aa3迅速、渐进性的还原反应，同时CBF增加高达200%。然而，在脑氧输送开始下降之前，CMRO2维持在接近正常的水平。这些大脑对氰化物的氧化反应可能是由于细胞内氧气供应重新分配到以氧气依赖方式呼吸的线粒体，或者是由于体内脑线粒体内的分支效应。
