Influence of naloxone on the increased sensitivity to propofol during hypovolemia in the rat.
OBJECTIVE
Hypovolemia has been shown to decrease the dose requirement for propofol. This increased effect has been explained partially by an increased end organ sensitivity to the anesthetic effect of propofol. We used the opioid blocking agent naloxone to test the hypothesis that endogenous opioids may be involved in this increased sensitivity.


METHODS
Thirty-two chronically instrumented rats were assigned randomly to either the hypovolemia (n = 16) or the control (n = 16) group.


METHODS
After pretreatment of each rat in the two groups with either intravenous saline (n = 8) or naloxone (3 mg/kg; n = 8), an intravenous infusion of propofol (150 mg x kg(-1) x hr(-1)) was given until 5 secs of electrical suppression of the electroencephalographic signal was observed. Return of righting reflex was used to assess depth of anesthesia, and the propofol blood concentration was determined simultaneously with high-performance liquid chromatography.


RESULTS
The mean propofol blood concentrations at the return of righting reflex were significantly lower in the hypovolemic animals compared with the controls within both naloxone-treated (2.1 +/- 0.2 microg/mL vs. 2.9 +/- 0.2 microg/mL; p < .01) and saline-treated (2.2 +/- 0.1 vs. 3.0 +/- 0.2 microg/mL; p < .01) rats. The mean concentrations were not different between the saline- and naloxone-treated rats either within the hypovolemic group or within the control group.


CONCLUSIONS
The results of our study indicate that it is unlikely that the increased end organ sensitivity to propofol during hypovolemia is mediated by endogenous opioids, because it was not reversed by naloxone.
De Paepe
P
P
Heymans Institute of Pharmacology, Ghent University, Belgium. Peter.DePaepe@rug.ac.be
Van Sassenbroeck
D K
DK
Belpaire
F M
FM
Buylaert
W A
WA
D018686:Anesthetics, Intravenous / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D006439:Hemodynamics / Q000187:drug effects; D020896:Hypovolemia / Q000097:blood*; D007262:Infusions, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D015742:Propofol / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D009292:Narcotic Antagonists; D009270:Naloxone; D015742:Propofol