title: A single small dose of ketamine prevents lung injury following hepatic ischemia-reperfusion in rabbits.
abstract: BACKGROUND
  Previous studies demonstrated that large-dose ketamine alleviated lipopolysaccharide-induced lung injury. We investigated whether a single small dose of ketamine could attenuate lung injury induced by hepatic ischemia-reperfusion (HIR) and, if so its underlying mechanisms.
  
  
  METHODS
  Thirty male New Zealand rabbits were randomized into three groups (n = 10 each): sham group (Group S), control group (Group C), and ketamine group (Group K). In Group S, hepatic portal vein (HPV) and inferior vena cava (IVC) were left unclamped and 0.9% saline 1 mL/kg was given intravenously. In Group K, ketamine 0.5 mg/kg (0.5 mg/mL) was given intravenously 10 minutes before cross-clamping of the HPV and the IVC. In Group C, 0.9% saline was given 10 minutes before the cross-clamping. The HPV and the IVC were cross-clamped with bulldog clamps and unclamped 60 minutes later in the Group K and the Group C. Blood pressure and pulse rate were recorded throughout the procedure. Rabbits were sacrificed 6 hours postoperatively. Lung W/D ratio was calculated and expression of tumor necrosis factor-α mRNA, intracellular adhesion molecule-1 mRNA, and nuclear factor kappa B (NF-κB)/p65 were quantitatively analyzed. Accumulation of neutrophils in lung tissues was also observed.
  
  
  RESULTS
  Small dose of ketamine alleviated the pulmonary edema, but not the systemic hypotension, induced by cross-clamping of the IVC and the HPV. Pretreatment with ketamine significantly reduced the increments of tumor necrosis factor-α mRNA, intracellular adhesion molecule-1 mRNA, and NF-κB/p65; and inhibited the aggregation of neutrophils in lung tissues following HIR.
  
  
  CONCLUSIONS
  0.5 mg/kg ketamine pretreatment showed significant protective effect on acute lung injury induced by HIR, which might be mediated by the NF-κB pathway.
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.forename: Xinliang
authors.initials: X
authors.lastname: Zhuang
authors.forename: Yachun
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000517:prevention & control*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007649:Ketamine / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply*; D008168:Lung / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D051996:Transcription Factor RelA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007649:Ketamine