Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury

Background and objective: Ventilator-induced lung injury (VILI) leads to airway epithelial cell apoptosis and lung inflammation. High tidal volume ventilation in vivo has been shown to induce MIP-2 production, lung neutrophil sequestration and apoptotic airway cell death. This study aimed to determine the effect of N-acetylcysteine (NAC), a scavenger of oxygen radicals, on lung inflammation and apoptosis in an in vivo model of VILI. Methods: Sprague-Dawley rats (n = 5 per group) were ventilated at low tidal volume (V-T 7 mL/kg) or high tidal volume (V-T 20 mL/kg) with or without administration of 140 mg/kg of intravenous NAC. Animals were ventilated for 30 min, 1 or 2 h, then allowed to recover for 2 h, at which time neutrophil infiltration, MIP-2, TNF-alpha and IL-6 in BAL fluid, as well as the percentage of apoptotic airway epithelial cells, were measured. Results:Ventilation at V-T 20 mL/kg increased oxidant release, as measured by serum isoprostane, and decreased lung glutathione, the major antioxidant in the lung. NAC treatment during ventilation at V-T 20 mL/kg prevented the decrease in lung glutathione and significantly lowered serum isoprostane levels, neutrophil infiltration, cytokines in the BAL and apoptosis in the airways as compared with animals ventilated at V-T 20 mL/kg without NAC (P < 0.05). Conclusions: These data point to an early role of oxidant-induced inflammation and apoptosis in VILI.