['Isoflurane may be protective in preclinical models of lung injury, but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. The authors hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome.', 'Wild-type mice were treated with isoflurane 1\u2009h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24\u2009h before mechanical ventilation (MV; tidal volume, 15\u2009ml/kg, 2\u2009h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1\u2009h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo.', 'Mice treated with isoflurane following exposure to inhaled endotoxin and before MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice after treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e., zona occludens 1) that was rescued by isoflurane treatment.'] Does isoflurane ameliorate Acute Lung Injury by Preserving Epithelial Tight Junction Integrity?