title: Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats.
abstract: OBJECTIVE
  The aim of this study was to document the effects of a new sedative agent, dexmedetomidine, on the mortality rate and inflammatory responses to endotoxin-induced shock in rats.
  
  
  METHODS
  Randomized laboratory study.
  
  
  METHODS
  University experimental laboratory.
  
  
  METHODS
  Fifty-seven male rats.
  
  
  METHODS
  The animals were randomly assigned to one of four groups. The endotoxemic group (n = 16) received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins). The saline control group (n = 10) was given saline alone. The dexmedetomidine alone group (n = 15) was treated identically to the control group but also received dexmedetomidine (infusion at 5 microg.kg(-1).hr(-1)) immediately after the injection of 0.9% saline. The dexmedetomidine-endotoxin group (n = 16) was treated identically to the endotoxemic group with the additional administration of dexmedetomidine (infusion at 5 microg.kg(-1).hr(-1)) immediately after endotoxin injection.
  
  
  RESULTS
  Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations measured during the observation. The mortality rate was assessed up to 8 hrs after endotoxin or saline injection. In addition, microscopic findings of lung tissue for each group were obtained at necropsy. Mortality rates 8 hrs after endotoxin injection were 94%, 10%, 0%, and 44% for the endotoxemic, saline control, dexmedetomidine alone, and dexmedetomidine-endotoxin groups, respectively. Hypotension and increases in plasma cytokine (tumor necrosis factor-alpha and interleukin-6) concentrations and infiltration of neutrophils in the airspace or vessel walls of the lungs were less in the dexmedetomidine-endotoxin group than in the endotoxemic group.
  
  
  CONCLUSIONS
  Dexmedetomidine reduced mortality rate and had an inhibitory effect on inflammatory response during endotoxemia. These findings suggest that dexmedetomidine administration may inhibit the inflammatory response.
authors.affiliation: Department of Emergency and Critical Care Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. ttaniyan@med.kanazawa-u.ac.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kidani
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kanakura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004731:Endotoxins / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D004731:Endotoxins; D006993:Hypnotics and Sedatives; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D020927:Dexmedetomidine