Acute Lung Injury (ALI) caused by reactive Chemicals in Animal Models: Diagnosis and Intervention
The types of acute lung injury (ALI) found in experimental animal models resemble remarkably well the key findings observed in accidentally exposed humans. However, generalization is often difficult as the site of injury and associated long-term sequelae are highly dependent on chemical-specific properties which include reactivity, water solubility and whether exposure is to a vapor or aerosol. Controlled acute inhalation studies in rats demonstrate that airway irritants cause a more lingering type of chronic obliterating bronchiolitis with/without tissue remodeling, whilst alveolar irritants are often associated with an life-threatening acute lung edema of rapid reversibility. Mechanistically-based countermeasures to mitigate alveolar edema following acute exposures to phosgene gas have been investigated in rats. Different treatment strategies were attempted following exposure; where feasible drugs were administered by nose-only inhalation, by intratracheal instillation or intraperitoneal injections. Neither treatment with dexamethasone, N- acetylcysteine, -tocopherol with or without ibuprofen favorably effected mortality. However, beneficial effects due to sedation were noticeable. Inadvertently imposed additional stresses required to administer these drugs post-phosgene exposure exacerbated dramatically the toxic response to phosgene. Thus, it appears as if factors reducing stress-related increases in hydrodynamic forces mitigate acute alveolar edema. These results caution against indiscriminant ad hoc use of drugs in the management of inhalational pulmonary injury.
Phosgene carbonyl chloride lung function nose-only exposure acute lung edema time course N-acetylcysteine dexamethasone alpha-tocopherol sedation.
Jurgen Pauluhn
Bayer Schering Pharma, 42096 Wuppertal, Germany
国际会议
上海
英文
77-101
2007-11-03（万方平台首次上网日期，不代表论文的发表时间）