Isoflurane preconditioning ameliorates endotoxin-induced acute lung injury and mortality in rats.
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.
Li
Qi Fang
QF
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhu
Ye Sen
YS
Jiang
Hong
H
Xu
Hui
H
Sun
Yu
Y
D000136:Acid-Base Equilibrium / Q000187:drug effects; D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D019610:Cytoprotection; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010100:Oxygen