title: Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats.
abstract: BACKGROUND
  Sepsis is associated with the highest risk of progression to acute lung injury or the acute respiratory distress syndrome. Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. Our study was designed to investigate the effect of ketamine on the endotoxin-induced acute lung injury in vivo.
  
  
  METHODS
  Adult male Wistar rats were randomly divided into 6 groups: saline controls; rats challenged with endotoxin (5 mg/kg) and treated with saline; challenged with endotoxin (5 mg/kg) and treated with ketamine (0.5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (50 mg/kg); saline injected and treated with ketamine (50 mg/kg). TNF-alpha, IL-6 and NF-kappa B were investigated in the tissues of the lung after 2 h. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated 6 h later.
  
  
  RESULTS
  We demonstrated that intravenous administration of endotoxin could provoke significant lung injury, which was characterized by increase of MPO activity and wet/dry weight ratio, TNF-alpha and IL-6 expression and NF-kappa B activation. Ketamine (5, 50 mg/kg) inhibited endotoxin-induced NF-kappa B activation. Ketamine only at a dose of 50 mg/kg inhibited TNF-alpha and IL-6 production, and decreased MPO activity and wet/dry weight ratio after endotoxin challenge.
  
  
  CONCLUSIONS
  Ketamine, only at a supra-anesthetic dosage, could inhibit endotoxin-induced pulmonary inflammation in vivo.
authors.affiliation: School of Medicine, Nanjing University and Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China. zbfcj@hotmail.com
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Duan
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: N
authors.initials: N
authors.lastname: Lin
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D004731:Endotoxins / Q000378:metabolism / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000517:prevention & control*; D055370:Lung Injury; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D018691:Excitatory Amino Acid Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D009195:Peroxidase