Clinical Drug Treatment of Edemagenic Gas-Induced Lung Injury

摘要

Studies were performed to address treatment against phosgene gas. Efficacy was judged by examining post-treatment (PTx) effects on pulmonary edema (PE) i.e. lung weight gain (LWG), survival rates (SR), odds ratios (OR), and glutathione (GSH) redox state, and lipid peroxidation (LP). N-acetylcysteine (NAC), ibuprofen (lBU), aminophylline (AMIN), and isoproterenol (ISO) were studied in the isolated perfused rabbit lung model (lPRLM) and mouse model. Intratracheal (IT) NAC delivered 1 h after phosgene exposure lowered pulmonary artery pressure (Ppa), LWG, leukotrienes (LTs), LP, and oxidized GSH. Using the lPRLM, AMIN after phosgene exposure significantly reduced LP and LTs, and LWG. Ptx with ISO in the IPRLM by combined intravascular (lV) or intratracheal (IT) route 1 h after phosgene lowered Ppa, tracheal pressure, LWG, and LTs. In mice lBU was administered i.p. 20 min after phosgene at 0, 3, 9, or 15 mg/mouse. At 5 h, a second lBU injection was given. The OR was 5 for the 9/4.5 lBU group at 12 h and 13 for the 15/7.5 mg IBU. lBU enhanced mouse SR by reducing PE, LP, and GSH depletion. Treatment of phosgene injury involves early intervention that reduces LP, maintains GSH, and prevents the release of LTs responsible for PE.