MECHANISM AND TREATMENT OF PHOSGENE POISONING

急性大量接触有毒气体仍然是一个面临的问题 职业医学和重症监护医学，不仅是由于孤立 涉及制造和使用氯气的工人的事故， 光气、二氧化氮、氨和二氧化硫，但也来自 意外中毒导致更多旁观者的暴露 在运输过程中会释放气体。已有很多关于慢性低血压的研究 暴露在这些药物中，但很少有关于病理生理学的工作 以及有毒气体引起的急性肺损伤和呼吸窘迫的治疗 吸气。这项拟议的研究将使用吸入光气暴露于 兔肺灌流作为急性毒气实验模型的实验研究 吸气。急性光气肺损伤的病理生理学将是 接受调查，包括急性支气管炎和肺 高血压是由于肺部产生花生四烯酸代谢产物所致。 如蛇床子素和白三烯，以及氧化性肺损伤是否来自 光气会耗尽肺内的谷胱甘肽。几种药理作用 药物(皮质类固醇、诺固醇抗炎药阻断 环氧合酶和脂氧合酶途径，蛋白酶抑制剂， 将研究β-肾上腺素能激动剂和前列腺素E_1)以 确定它们在关注肺水肿形成方面的有效性。N-乙酰 谷胱甘肽前体半胱氨酸对氧化性肝的治疗作用 中毒剂量的对乙酰氨基酚的损害将作为治疗方法进行评估 通过确保充足的肺谷胱甘肽供应来实现光气中毒 与光气反应，防止其与细胞膜和细胞结合 酵素。食品添加剂、抗氧化剂、丁基羟基等药物 将研究升高肺谷胱甘肽的苯甲醇(BHA)以确定 是否有可能对光气中毒进行化学预防。结果是 本研究可为生理学推荐提供依据。 急性有毒气体吸入致人氧化性肺损伤的声音治疗。

Acute massive toxic gas exposure continues to be a problem facing occupational medicine and critical care medicine, not only due to isolated accidents involving workers in the manufacturing and use of chlorine, phosgene, nitrogen dioxide, ammonia, and sulfer dioxide, but also from exposure of larger bystander populations resulting from accidental toxic gas release during transportation. Much research exists on chronic low level exposure to these agents, but there is little work on pathophysiology and therapy of acute lung damage and respiratory distress from toxic gas inhalation. The proposed research will use inhaled phosgene exposure of an isolated perfused rabbit lung as a laboratory model for acute toxic gas inhalation. The pathophysiology of acute phosgene lung damage will be investigated, including whether acute broncho-constriction and pulmonary hypertension are due to lung production of arachidonic acid metabolites such as thomboxane and leukotrienes, and whether oxidant lung damage from phosgene causes depletion of lung glutathione. Several pharmacologic agents (corticosteroids, nosteroidal anti-inflammatory agents blocking cyclooxygenase and lipoxygenase pathways, protease inhibitors, beta-adrenergic agonists, and prostaglandin El) will be studied to determine their usefulness in attentuating lung edema formation. N-acetyl cysteine, a precursor of glutathione effective in treating oxidant liver damage from toxic doses of acetaminophen, will be evaluated as therapy for phosgene poisoning by insuring a sufficient supply of lung glutathione to react with phosgene and prevent its combination with membranes and cellular enzymes. Drugs such as the food additive antioxidant butylated hydroxy anisol (BHA) which elevate lung glutathione will be studied to determine whether chemoprophylaxis of phosgene poisoning is possible. The results of this research can provide a foundation for recommending physiologically sound therapy of oxidant lung damage from acute toxic gas inhalation in man.