Mechanism of Chemical Action and Treatment of Cyanide Poisoning

摘要

During the third year of the contract, the authors conducted experiments to determine: (1) the effect of cyanide on hepatocyte oxygen consumption, (2) the disposition of cyanide with sodium nitrite, 4-dimethylaminophenol (DMAP), cobaltous chloride, and sodium sulfite antidotes, (3) antidotal effectiveness with primate cells, (4) the efficacy of other drugs and cyanide antidotes in the system, and (5) the characteristics of the sulfurtransferase activity in erythrocytes with Na2S2O3 antidote. The half-maximal concentrations for cyanide-induced reduction in O2 consumption, ATP, ATP/ADP, and urea synthesis were determined to be 0.078, 0.20-0.24, 0.14, and 0.11 mM, respectively. The K sub m for inhibition of O2 consumption is in the range of plasma levels of cyanide at lethality. These levels also produce cytochrome oxidase inhibition in liver tissue in vivo. The results were consistent with the hypothesis that cytochrome oxidase inhibition initiates cytotoxicity and suggest that isolated hepatocyte systems are a good model for in vivo response.