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羟钴胺素对氰化物中毒解毒效果的体外验证

In vitro demonstration of the antidotal efficacy of hydroxocobalamin in cyanide poisoning.

作者信息

Riou B, Baud F J, Astier A, Barriot P, Lecarpentier Y

机构信息

Institut National de la Santé et de la Recherche Médicale U275, LOA-ENSTA-Ecole Polytechnique, Palaiseau, France.

出版信息

J Neurosurg Anesthesiol. 1990 Dec;2(4):296-304. doi: 10.1097/00008506-199012000-00008.

DOI:10.1097/00008506-199012000-00008
PMID:15815367
Abstract

The effects of sodium cyanide (1 mM) and the antidotal action of hydroxocobalamin (1 mM) were studied on rat cardiac papillary muscle. A 10-min period of exposure to cyanide induced a marked decrease in inotropy as shown by a decrease in the maximum unloaded shortening velocity (Vmax: 64 +/- 11% of precyanide values, p <0.01) and active isometric force (AF/s: 35 +/- 13%, p <0.01). The impairment of contraction-relaxation coupling under low load and the nearly complete disappearance of the load sensitivity of relaxation suggested a decrease in sarcoplasmic reticulum function. The proportional acceleration in isometric relaxation suggested a decrease in myofilament calcium sensitivity. There was a nearly complete recovery from cyanide poisoning after 5 min of exposure to hydroxocobalamin, whereas in a control group receiving cyanide alone, the mechanical parameters remained unchanged or were further impaired. The effects of hydroxocobalamin developed very quickly, beat to beat. The main toxic target of cyanide is brain and heart cytochrome oxidase, and brain damage appears only a few minutes after the onset of anoxia. Because hydroxocobalamin is a rapid and powerful antidote, it may be useful in the treatment of acute cyanide poisoning.

摘要

研究了氰化钠(1 mM)对大鼠心脏乳头肌的影响以及羟钴胺素(1 mM)的解毒作用。暴露于氰化物10分钟导致心肌收缩力显著下降,表现为最大无负荷缩短速度降低(Vmax:为氰化物暴露前值的64±11%,p<0.01)和主动等长力降低(AF/s:35±13%,p<0.01)。低负荷下收缩-舒张偶联的受损以及舒张负荷敏感性几乎完全消失提示肌浆网功能下降。等长舒张的比例加速提示肌丝钙敏感性降低。暴露于羟钴胺素5分钟后,氰化物中毒几乎完全恢复,而在仅接受氰化物的对照组中,力学参数保持不变或进一步受损。羟钴胺素的作用起效非常快,逐搏显现。氰化物的主要毒性靶点是脑和心脏细胞色素氧化酶,缺氧发作后几分钟才会出现脑损伤。由于羟钴胺素是一种快速且强效的解毒剂,它可能对急性氰化物中毒的治疗有用。

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