Dose effects of propofol on hemodynamic and cytokine responses to endotoxemia in rats.
OBJECTIVE
Our previous studies have demonstrated that propofol inhibits hypotension, metabolic acidosis, and cytokine responses and reduces mortality in endotoxemic rats. The purpose of this study was to elucidate whether these beneficial effects of propofol on hemodynamics and cytokine responses were dose related.


METHODS
Forty-eight rats were divided at random among four equal groups: groups S, M, and L received intravenous propofol administration (5, 10, and 20 mg.kg(-1).h(-1), respectively) immediately after endotoxin (Escherichia coli endotoxin; 15 mg.kg(-1), i.v.) was given. Group E received endotoxin alone. We assessed hemodynamics and plasma cytokine [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6] concentrations for 5 h following endotoxin injection.


RESULTS
Systolic arterial pressure (SAP) was significantly higher at 4 and 5 h in groups S and M than in group E (P < 0.05), although SAP decreased progressively in all groups. Endotoxin injection increased the TNF-alpha and IL-6 concentrations in all groups. The increase in TNF-alpha concentrations at 2 h was significantly lower in group M than in group E (P < 0.05). On the other hand, the increase in IL-6 concentration at 5 h was significantly lower in groups M and L than in group E (P < 0.05).


CONCLUSIONS
The effects of propofol on blood pressure and cytokine responses were influenced by the dose of propofol, although the relationship did not follow simple linearity.
Takemoto
Yasuhiro
Y
Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000097:blood* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018686:Anesthetics, Intravenous; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015742:Propofol