Sevoflurane reduces severity of acute lung injury possibly by impairing formation of alveolar oedema

Abstract

Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium-potassium-adenosine-triphosphatase pump (Na +/K +-ATPase). Water follows to maintain iso-osmolar conditions and to keep alveoli dry. We postulated that the volatile anaesthetic sevoflurane would impact oedema resolution positively in an in-vitro and in-vivo model of ALI. Alveolar epithelial type II cells (AECII) and mixed alveolar epithelial cells (mAEC) were stimulated with 20μg/ml lipopolysaccharide (LPS) and co-exposed to sevoflurane for 8h. In-vitro active sodium transport via ENaC and Na +/K +-ATPase was determined, assessing 22sodium and 86rubidium influx, respectively. Intratracheally applied LPS (150μg) was used for the ALI in rats under sevoflurane or propofol anaesthesia (8h). Oxygenation index (PaO 2/FiO 2) was calculated and lung oedema assessed determining lung wet/dry ratio. In AECII LPS decreased activity of ENaC and Na +/K +-ATPase by 17·4%±13·3% standard deviation and 16·2%±13·1%, respectively. These effects were reversible in the presence of sevoflurane. Significant better oxygenation was observed with an increase of PaO 2/FiO 2 from 189±142mmHg to 454±25mmHg after 8h in the sevoflurane/LPS compared to the propofol/LPS group. The wet/dry ratio in sevoflurane/LPS was reduced by 21·6%±2·3% in comparison to propofol/LPS-treated animals. Sevoflurane has a stimulating effect on ENaC and Na +/K +-ATPase in vitro in LPS-injured AECII. In-vivo experiments, however, give strong evidence that sevoflurane does not affect water reabsorption and oedema resolution, but possibly oedema formation. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.