Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats.
OBJECTIVE
To clarify the effects of posttreatment with propofol administration on mortality rate and cytokine responses to endotoxin-induced shock in rats.


METHODS
Randomized prospective laboratory study.


METHODS
University laboratory.


METHODS
Thirty-three male rats.


METHODS
Animals were randomly assigned to one of three groups (n = 11 per group): a) endotoxemic group, receiving intravenous Escherichia coli endotoxin (20 mg/kg over 2 mins); b) early posttreatment group, treated identically to the endotoxemic group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg x kg(-1) x hr(-1)) 1 hr after the injection of endotoxin; and c) late posttreatment group, treated identically to the endotoxemic group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg x kg(-1) x hr(-1)) 2 hrs after the injection of endotoxin.


RESULTS
Hemodynamics and arterial blood gases were recorded, and mortality rate and plasma cytokine concentrations were calculated for the 5-hr observation. The mortality rate 5 hrs after endotoxin injection was 73% for the endotoxic, 9% for the early posttreatment, and 36% for the late posttreatment groups. The mortality rate for the early posttreatment group was significantly lower than that for the other groups. The increases in plasma cytokine (tumor necrosis factor-alpha and interleukin-6 and -10) concentrations were less for the early posttreatment group than the other two groups.


CONCLUSIONS
The early posttreatment of propofol after endotoxin injection drastically reduced the mortality rate of rats and attenuated their cytokine responses. Moreover, propofol attenuated the production of tumor necrosis factor-alpha. These findings suggest that propofol administration may be beneficial during sepsis.
Taniguchi
Takumi
T
Department of Emergency and Critical Care Medicine, School of Medicine, Kanazawa University, Kanazawa, Japan. taniyan@med.kanazawa-u.ac.jp
Kanakura
Hiroko
H
Yamamoto
Ken
K
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D010100:Oxygen / Q000097:blood; D015742:Propofol / Q000008:administration & dosage*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D010100:Oxygen; D015742:Propofol