Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.