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首页> 外文期刊>Toxicology and Applied Pharmacology >Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation
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Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

机译：氯丁吸入兔模型中的急性肺损伤和持续小气道疾病

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Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. (C) 2016 Elsevier Inc. All rights reserved.
机译：氯是一种肺部毒物，人类可能会因事故或故意释放而接触到它。氯气吸入对人类和动物模型的急性影响已经得到了很好的描述，但对急性高水平氯气暴露的持续影响知之甚少。特别是，目前还缺乏能够复制人类长期效应的动物模型。在这里，我们报告了一种兔子模型的开发，在该模型中，可以评估吸入氯气的急性和持续影响。雄性新西兰大白兔暴露于氯气中，同时对肺部进行机械通气。氯气暴露后，兔子被拔管，并在暴露于800ppm氯气4分钟后存活24小时以研究急性效应，或在暴露于400ppm氯气8分钟后存活7天以研究长期效应。吸入800ppm氯4分钟后6或24小时观察到的急性效应包括低氧血症、肺水肿、气道上皮损伤、炎症、基线肺力学改变以及吸入乙酰甲胆碱后气道高反应性。吸入400ppm氯8分钟后7天，兔子出现轻度低氧血症、压力-容积环面积增加和气道高反应性。氯气暴露7天后的肺组织学检查显示小气道异常，包括炎症和散发性闭塞性细支气管炎病变。免疫染色显示这些部位的上皮细胞中缺乏棒状细胞和纤毛细胞。这些结果表明，小气道疾病可能是急性氯气暴露后持续呼吸异常的重要组成部分。这种非啮齿类氯气暴露模型对于研究急性氯气暴露的持续影响和评估氯气所致肺损伤对策的有效性应该是有用的。（C） 2016爱思唯尔公司版权所有。

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