The antiinflammatory effects of propofol in endotoxemic rats during moderate and mild hypothermia

Abstract

We previously found that propofol attenuated the mortality rate and inflammatory responses during endotoxemia in rats; however, whether propofol retains its antiinflammatory effects during hypothermia has not been determined. We investigated the effects of propofol on endotoxemic rats subjected to moderate or mild hypothermia. Male Wistar rats (n = 88) were anesthetized intraperitoneally with pentobarbital sodium and assigned to one of two protocols: one representing moderate hypothermia (30 degrees -32 degrees C) and the other representing mild hypothermia (33 degrees -35 degrees C). Each protocol included four equal-sized groups: group A, Escherichia coli endotoxin (15 mg x kg(-1), i.v.) and normothermia; group B, propofol (10 mg x kg(-1) x h(-1), i.v.) and normothermia after endotoxin injection; group C, endotoxin (15 mg x kg(-1), i.v.) and hypothermia; and group D, propofol (10 mg x kg(-1) x h(-1), i.v.) and hypothermia after endotoxin injection. Rats then were warmed or cooled to maintain rectal temperatures as above for 6 h. The mortality rate was assessed up to 6 h after endotoxin injection. In addition, we assessed hemodynamics, acid-base status, and plasma cytokine concentrations. Endotoxemic rats developed hypotension and metabolic acidosis as well as increased plasma cytokine concentrations. Mortality rates 6 h after endotoxin injection were 70%, 40%, 10%, and 0% for groups A-D, respectively, at moderate hypothermia. Propofol administration to endotoxemic rats with hypothermia, whether moderate or mild, also attenuated the high mortality rate, metabolic acidosis, and elevation of cytokines, but these effects were not superior to those of hypothermia alone. During hypothermia, propofol administration does not have additive beneficial antiinflammatory effects.