Pre-treatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke

There is little information on which medications may increase heat stroke(HS) susceptibility/severity. We investigated whether the Non-steroidal anti-inflammatory drug(NSAID) indomethacin(INDO) increases HS severity in a rodent model. Core temperature(T_c) of male, C57BL/6J mice(N= 45) was monitored continuously and mice were given a dose of INDO(low (LO) dose 1mg/kg or high (HI) dose 5mg/kg in flavored treat) or vehicle(flavored treat) prior to heating. HS animals were heated to 42.4°C and sacrificed at three time points for histological, molecular, and metabolic analysis: onset of HS(maximal core temperature, T_c,Max), 3 hours of recovery(minimal core temperature or hypothermia depth, HYPO), and 24 hours of recovery(24hrs). Non-heated(control) animals underwent identical treatment in the absence of heat. INDO(LO or HI) had no effect on physiological indicators of performance(e.g. time to T_c,Max, thermal area, cooling time) during heating or recovery. HI doses of INDO resulted in 45% mortality rate by 24hrs(HI INDO +HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO +HS in both survivors/non-survivors. HI INDO +HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at T_c,Max, HYPO, and 24hrs with HS, however there was no additive effect with INDO +HS. Further, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO +HS. This suggests there is an increase in morbidity risk with INDO +HS, likely resulting from significant gut injury.

from Physiology via xlomafota13 on Inoreader http://ift.tt/2t03q8K
via IFTTT