亚致死氰化物毒性兔模型中的肌肉内 cobinamide 亚硫酸盐。
Intramuscular cobinamide sulfite in a rabbit model of sublethal cyanide toxicity.
机构信息
Laser Microbeam and Medical Program, Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
出版信息
Ann Emerg Med. 2010 Apr;55(4):352-63. doi: 10.1016/j.annemergmed.2009.12.002. Epub 2010 Jan 4.
STUDY OBJECTIVE
Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity.
METHODS
New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5).
RESULTS
Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals.
CONCLUSION
Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.
研究目的
火灾和工业暴露中氰化物的暴露以及恐怖分子故意氰化物中毒导致大量人员伤亡是持续存在的威胁。目前治疗氰化物中毒的方法必须静脉内给药，并且对于大量人员接触氰化物的情况，没有快速的治疗方法。钴胺酰胺是一种氰化物亲和力极高的钴胺素（维生素 B12）类似物，比钴胺素更易溶于水。我们研究了肌内钴胺酰胺亚硫酸盐在亚致死剂量氰化物暴露动物模型中逆转氰化物毒性引起的生理变化的用途，并确定肌内钴胺酰胺亚硫酸盐注射迅速逆转氰化物毒性生理效应的能力。
方法
新西兰白兔静脉内给予 10mg 氰化钠，持续 60 分钟。同时进行定量漫反射光学光谱和连续波近红外光谱监测组织氧合血红蛋白和脱氧血红蛋白浓度，并测量血液氰化物水平和钴胺酰胺水平。在氰化物输注完成后，立即向兔肌内注射钴胺酰胺亚硫酸盐（n=6）或无效载体（对照组，n=5）。
结果
肌内给药导致钴胺酰胺迅速动员，并非常有效地逆转了氰化物对氧合血红蛋白和脱氧血红蛋白提取的生理效应。在对照组中，恢复到中枢神经系统基线值的 63%的时间平均为 1032 分钟，而在钴胺酰胺组中为 9 分钟，差异为 1023 分钟（95%置信区间为 116 至 1874 分钟）。在肌肉组织中，恢复时间分别为 76 和 24 分钟，差异为 52 分钟（95%置信区间为 7 至 98 分钟）。红细胞氰化物水平在钴胺酰胺亚硫酸盐处理的动物中比在对照组中更快地恢复到正常水平。
结论
肌内钴胺酰胺亚硫酸盐迅速有效地逆转了氰化物中毒的生理效应，这表明可以为大量人员接触氰化物的情况开发一种紧凑的氰化物解毒试剂盒。
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