• Joshua A Englert, Alvaro A Macias, Diana Amador-Munoz, Miguel Pinilla Vera, Colleen Isabelle, Jiazhen Guan, Brady Magaoay, Margarita Suarez Velandia, Anna Coronata, Awapuhi Lee, Laura E Fredenburgh, Deborah J Culley, Gregory Crosby, and Rebecca M Baron.
• From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (J.A.E., D.A.-M., M.P.V., C.I., J.G., B.M., M.S.V., A.C., A.L., L.E.F., R.M.B.) and Department of Anesthesiology, Perioperative, and Pain Medicine (A.A.M., D.J.C., G.C.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
• Anesthesiology. 2015 Aug 1;123(2):377-88.

BackgroundIsoflurane 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.MethodsWild-type mice were treated with isoflurane 1 h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24 h before mechanical ventilation (MV; tidal volume, 15 ml/kg, 2 h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1 h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo.ResultsMice 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.ConclusionsIsoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

21 keywords...

hide…