Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs.
Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs.
复制标题
暴露后用鼻阿托品溴化物治疗可防止豚鼠微滴吸入沙林。
DOI：
10.1016/j.taap.2009.06.002
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发表时间：
2009
影响因子：
3.8
通讯作者：
Nambiar,MadhusoodanaP
中科院分区：
文献类型：
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作者：
Che,MagnusM;Conti,Michele;Chanda,Soma;Boylan,Megan;Sabnekar,Praveena;Rezk,Peter;Amari,Ethery;Sciuto,AlfredM;Gordon,RichardK;Doctor,BhupendraP;Nambiar,MadhusoodanaP
我们评估了不穿过血脑屏障的鼻用甲基溴阿托品（AMB）对沙林吸入暴露的保护作用。采用微滴吸入暴露技术，将年龄和体重匹配的雄性豚鼠暴露于846.5 mg/m3沙林中4分钟。这个剂量的存活率是20%。暴露后鼻用AMB （2.5 mg/kg， 1分钟）完全防止沙林引起的毒性（100%存活率）。用鼻用AMB治疗的动物肌肉震颤的发生减少。暴露后鼻用AMB治疗也使沙林暴露后血氧饱和度和心率的急性下降正常化。鼻腔AMB治疗的动物在沙林暴露后血液AChE和BChE活性的抑制降低，表明生存增加了沙林的代谢或AChE的表达。暴露于沙林并接受鼻用AMB治疗的动物体重减轻与生理盐水对照组相似。暴露于沙林和随后的鼻用AMB治疗后，肺副叶或气管水肿没有观察到差异。总支气管肺泡灌洗液（BALF）蛋白是肺损伤的生物标志物，其变化趋势与生理盐水对照组相似。鼻用AMB暴露后表面活性剂水平恢复正常，与生理盐水对照组相似。鼻用AMB暴露后碱性磷酸酶水平降低。综上所述，这些数据表明鼻腔AMB阻断了丰富的气道分泌和外周胆碱能作用，并防止致命的吸入暴露于沙林，从而提高了生存率。
We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood–brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m3sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.