Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats.
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.
Taniguchi
Takumi
T
Department of Emergency and Critical Care Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. ttaniyan@med.kanazawa-u.ac.jp
Kidani
Yoko
Y
Kanakura
Hiroko
H
Takemoto
Yasuhiko
Y
Yamamoto
Ken
K
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
D004731:Endotoxins; D006993:Hypnotics and Sedatives; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D020927:Dexmedetomidine