title: The preconditioning pulmonary protective effect of volatile isoflurane in acute lung injury is mediated by activation of endogenous iNOS.
abstract: OBJECTIVE
  There is still a lack of evidence to support the use of specific anesthetic agents during major operations that could affect the development of postoperative acute lung injury (ALI). This study determined the protective effect of inhaled isoflurane in a rat model of endotoxin-induced ALI.
  
  
  METHODS
  Rats were exposed to volatile isoflurane (1.5 % in oxygen) or pure oxygen via a facemask for 2 h. After a 3-h recovery period, rats were reanesthetized and ALI was induced by intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg in 0.5 ml saline). In some animals, a specific inducible nitric oxide synthase (iNOS) inhibitor, 1400W, (10 mg/kg, i.p.) was administered before exposure to isoflurane. Animals were sacrificed 12 h later for analysis. Pulmonary artery vasomotor function and alveolocapillary permeability were assessed. Expression of iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed.
  
  
  RESULTS
  The maximal relaxation response to acetylcholine was significantly potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were attenuated in the lung tissue obtained from rats receiving isoflurane. Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung preexposed to isoflurane. However, these pulmonary protective effects of isoflurane were significantly abolished by pretreatment with 1400W.
  
  
  CONCLUSIONS
  Pretreatment with volatile isoflurane attenuated inflammatory process in the lung tissue of rats with LPS-induced ALI, and this preconditioning pulmonary protective effect was mainly mediated by activation of endogenous iNOS in the lung.
authors.affiliation: Department of Anesthesiology, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Pang
authors.forename: Bing-Shuo
authors.initials: BS
authors.lastname: Chen
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Li
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Huang
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Chang
authors.forename: Chen-Fuh
authors.initials: CF
authors.lastname: Lam
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Tsai
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D055371:Acute Lung Injury / Q000201:enzymology / Q000517:prevention & control*; D000578:Amidines / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D039481:CD11b Antigen / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007530:Isoflurane / Q000627:therapeutic use*; D007537:Isometric Contraction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000578:Amidines; D018685:Anesthetics, Inhalation; D001596:Benzylamines; D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D014665:Vasodilator Agents; D007530:Isoflurane; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine