Abstract
The effects of isoflurane pretreatment on pulmonary proinflammatory cytokines and survival in severe endotoxin-induced acute lung injury (ALI) have not been studied systemically. We investigated the effect of preadministration of isoflurane on ALI induced by lipopolysaccharide (LPS) in rats. Male Sprague-Dawley rats weighing 250-300 g were randomly assigned to 1 of 4 groups: sham rats (injected intraperitoneally [IP] with saline) pretreated with vehicle (100% O(2)) (sham-vehicle); sham rats pretreated with isoflurane (sham-ISO); LPS rats (injected IP with LPS) pretreated with vehicle (vehicle-LPS); and LPS rats pretreated with isoflurane (ISO-LPS). Endotoxemia was induced by IP injection of LPS. Isoflurane 1.4% was administered 30 min before LPS injection. The animals were then observed for 6 h. We monitored arterial blood pressure, heart rate, and blood gas. The extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye extravasation, and histologic examination. We also measured pulmonary nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels. In addition, survival statistics and pulmonary inducible NO synthase (iNOS) gene expression were also determined. LPS caused systemic hypotension and severe ALI, as evidenced by the increases in the extent of ALI, impairment of pulmonary functions, and increases in pulmonary NO, TNF-alpha, IL-1beta, and IL-6. Isoflurane preconditioning mitigated systemic hypotension and the development of ALI. Isoflurane preconditioning also attenuated the LPS-induced increases in pulmonary nitrate/nitrite and proinflammatory cytokine release and improved survival of rats with severe sepsis. The expression of iNOS was upregulated by LPS and reduced by isoflurane pretreatment. Isoflurane preconditioning can attenuate pulmonary proinflammatory cytokine release and decrease the mortality induced by severe sepsis. Early protection seems to be mediated partly through inhibition of iNOS-NO pathway activation.
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