Isoflurane Ameliorates Acute Lung Injury by Preserving Epithelial Tight Junction Integrity

Authors:
Open Access
Publisher website
Google Scholar
Abstract
In a murine two-hit model of endotoxin-induced inflammation followed by ventilator-induced lung injury, isoflurane exposure before mechanical ventilation ameliorated the ventilator-induced lung injury by improving both lung mechanics and vascular leakage without changing inflammatory responses. In mouse lung tissue and in lung epithelial cells injured similarly to the in vivo model, decrease of a key tight junction protein (zona occludens 1) was prevented with isoflurane preconditioning. Supplemental Digital Content is available in the text. Background: 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. Methods: Wild-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. Results: 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. Conclusions: Isoflurane 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.

This publication has 49 references indexed in Scilit: