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麻醉豚鼠致死性梭曼中毒的阿托品与肟类治疗:HLö 7二甲磺酸盐与HI 6二氯化物的比较

Atropine and oxime treatment in lethal soman poisoning of anaesthetized guinea-pigs: HLö 7 dimethanesulfonate versus HI 6 dichloride.

作者信息

Worek F, Szinicz L

机构信息

Institute of Pharmacology and Toxicology, Federal Armed Forces Medical Academy, BSW, Garching, Germany.

出版信息

Pharmacol Toxicol. 1993 Jan;72(1):13-21. doi: 10.1111/j.1600-0773.1993.tb01332.x.

Abstract

The oxime HI 6 is considered to be effective in soman poisoning and less effective in tabun poisoning. Recently, HLö 7 was shown to reactivate acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the efficacy of HLö 7 and HI 6 was compared in soman poisoned guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the a. carotis, v. jugularis and trachea were cannulated. After base line measurements soman 0.08 mg/kg (= 5 x LD50) or 0.16 mg/kg (= 10 x LD50) was injected intravenously, 2 min. later the antidotes were applied intravenously: HLö 7 0.03 or 0.1 mmol/kg, HI 6 0.03 or 0.1 mmol/kg, atropine 10 mg/kg, or a combination of atropine and an oxime. Respiratory and circulatory parameters were recorded for 60 min. or until the death of the animal. The injection of 5 x LD50 soman resulted in a rapid respiratory arrest followed by circulatory failure in the soman and soman plus oxime groups (survival time about 7 min). Atropine restored the circulatory parameters to base line but was unable to provide a sufficient respiratory function (survival time 26 min.). The combination therapy with atropine plus HLö 7 or HI 6 improved the respiration sufficiently, restored the circulation completely, and prolonged the survival time to about 50 min. Atropine treatment was insufficient in animals poisoned with 10 x LD50 soman. The combination of atropine and HLö 7 or HI 6 improved respiration, circulation, and survival time to various extent. Despite of the striking therapeutic effect no reactivation of erythrocyte AChE by the antidotes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

肟HI 6被认为对梭曼中毒有效,而对塔崩中毒效果较差。最近,HLö 7被证明能使被梭曼和塔崩抑制的乙酰胆碱酯酶(AChE)重新活化。因此,在梭曼中毒的豚鼠中比较了HLö 7和HI 6的疗效。用乌拉坦(1.8 g/kg)麻醉雌性派珀布赖特-白色豚鼠,对颈动脉、颈静脉和气管进行插管。在进行基线测量后,静脉注射0.08 mg/kg(=5×半数致死剂量)或0.16 mg/kg(=10×半数致死剂量)的梭曼,2分钟后静脉给予解毒剂:HLö 7 0.03或0.1 mmol/kg、HI 6 0.03或0.1 mmol/kg、阿托品10 mg/kg,或阿托品与肟的组合。记录呼吸和循环参数60分钟或直至动物死亡。注射5×半数致死剂量的梭曼后,梭曼组和梭曼加肟组迅速出现呼吸停止,随后出现循环衰竭(存活时间约7分钟)。阿托品使循环参数恢复到基线,但无法提供足够的呼吸功能(存活时间26分钟)。阿托品加HLö 7或HI 6的联合治疗充分改善了呼吸,完全恢复了循环,并将存活时间延长至约50分钟。阿托品治疗对10×半数致死剂量梭曼中毒的动物不足。阿托品与HLö 7或HI 6的组合在不同程度上改善了呼吸、循环和存活时间。尽管有显著的治疗效果,但未观察到解毒剂使红细胞AChE重新活化。(摘要截短至250字)

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