Demnati R, Fraser R, Martin JG, Plaa G, Malo JL
We assessed the effects of dexamethasone on functional and histological changes after acute exposure to a high level of chlorine gas in an animal model of reactive airways dysfunction syndrome (RADS). Sprague-Dawley male rats were exposed to 1500 ppm of chlorine for 5 min and treated with either dexamethasone (dex; 300 micrograms/kg/day) or saline intraperitoneally for 7 days. Lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), airway wall morphometric measurements, and bronchoalveolar lavage (BAL) cells were assessed over a 2-week period after exposure. Dex administration significantly attenuated both chlorine-induced increased RL and chlorine-induced increased responsiveness to methacholine compared with saline: -2.7 +/- 6.8% vs 102.3 +/- 36.6% change from baseline RL (P<0.01) and 2.5 +/- 0.6 mg/ml vs 1.2 +/- 0.7 mg/ml in the MCh concentration required to double the RL from baseline (P<0.01). There was a tendency, albeit nonsignificant, for improvement in some indices of epithelial injury. Dex significantly attenuated the postexposure neutrophilic cellular response in BAL 1 day after exposure (15.8 +/- 4.9% neutrophils in the dex group vs 49.8 +/- 2.7% neutrophils in the saline group) (P<or = 0.001). Our results show that dex administration helps maintain pulmonary function, reduces BAL inflammatory cell number, and tends to improve some morphometric airway wall structure parameters in rats exposed to chlorine.
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Quebec, Canada.