Alveolar epithelial type II cells (AECII) and mixed alveolar epit

Alveolar epithelial type II cells (AECII) and mixed alveolar epithelial cells (mAEC) were stimulated with 20 µg/ml lipopolysaccharide (LPS) and co-exposed to sevoflurane for 8 h. In-vitro active sodium transport via ENaC and Na+/K+-ATPase was determined, assessing 22sodium and 86rubidium influx, respectively. Intratracheally applied LPS (150 µg) was used for the ALI in rats under sevoflurane or propofol anaesthesia (8 h). Oxygenation index (PaO2/FiO2) 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 PaO2/FiO2 from 189 ± 142 mmHg to 454 ± 25 mmHg after 8 h in the sevoflurane/LPS compared to the propofol/LPS group. The wet/dry ratio in sevoflurane/LPS selleck kinase inhibitor was reduced by 21·6% ± 2·3% selleck compound 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. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a major cause of acute respiratory failure in critically ill patients [1]. The mortality of ARDS has remained high since its first description by Ashbaugh and colleagues [2], although lung protective ventilatory strategies have reduced mortality from 60–70% to 35–40% [3,4]. While drug treatment is investigated intensively,

no pharmacological approach has yet been established [5–8]. ALI/ARDS is characterized by capillary leak and reduced fluid reabsorption, resulting in lung oedema. The level of decreased rate of fluid clearance has significant prognostic value for morbidity and mortality [9]. In addition to reduced fluid reabsorption, protein clearance is also impaired. As demonstrated in patients with ARDS, non-survivors have three Cobimetinib clinical trial times higher alveolar protein concentrations than survivors [10,11]. Several studies have tried to detect the underlying mechanism of impairment of alveolar fluid clearance in ALI/ARDS and various pathways have been suggested [12–14]. According to experimental evidence, the active sodium (Na+) transport is thereby the most important ion transport mechanism involved in fluid reabsorption out of the alveolar space [15,16]. The broadly accepted paradigm for Na+ transport in the alveoli is a two-step process: Na+ enters the cell by epithelial amiloride-sensitive Na+-channels (ENaC) located at the apical surface and is extruded by basolaterally located sodium–potassium–adenosine–triphosphatase pumps (Na+/K+-ATPases) [17,18].

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