Ibuprofen increases resistance to exertional heat stroke in female mice

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The impact of nonsteroidal anti‐inflammatory drugs (NSAIDs) on the severity or susceptibility to exertional heat stroke (EHS) is unknown. Previous studies have demonstrated that in humans, thermogenic responses to endurance exercise are suppressed by NSAIDs and that NSAIDs increase the endurance time to exhaustion in rats. However, NSAIDs have also been shown to contribute to organ damage in both severe exercise alone and in conditions of heat stress alone, which may limit performance.METHODSIn this study, we determined the effects of ibuprofen administration (IBU) on exercise performance and resistance to heat stroke in male and female mice in an established model of exertional heat stroke (EHS). Two days prior to EHS, the mice were given continuous IBU‐loaded chow (ad libitum) at 375 mg/kg (N = 7–8) compared to controls (N =44). To induce EHS, the mice ran a preprogrammed incremental exercise protocol using a forced running wheel in an environmental chamber at 37.5°C/35% RH, until a symptom‐limited max was reached (loss of consciousness). The EHS protocol was defined by an incremental exercise phase (IP) and a steadystate exercise phase (SP). During the IP, wheel speeds were increased every 10 min until core temperature (Tc) = 41°C. This was followed by a SP phase, in which speed was maintained until a symptom‐limited endpoint.RESULTSAll groups ran to nearly identical peak Tcs (42.2–42.4°C). IBU‐treated female mice exercised longer in heat, prior to collapse, compared to controls (223 vs. 176 min; P = 0.0018), but there was no significant effect in males (133 min vs 124 min). Time in the IP was higher in the IBU‐female mice compared to controls (181 vs 131; P=0.0018). Though the duration of the SP phase did not change in any group, female IBU mice ran at significantly higher power outputs during the SP phase compared to controls (females: 34.5 mW vs 27.4 mW, P=0.0004) demonstrating a lower rate of heat accumulation for a given rate of external power expended.CONCLUSIONSThese data demonstrate that in female mice, short‐term IBU treatment improves exercise performance in the heat and delays the onset of EHS. The results are consistent with the hypothesis that a component of the temperature elevation seen in EHS arises from endogenous pyrogen production that can be blocked by IBU. The lack of similar responsiveness in males may reflect greater sensitivity to EHS in male vs. female mice and predominance of other mechanisms limiting performance in the heat. Authors' views not official US Army or DoD policy. W81XWH‐15‐2‐0038Support or Funding InformationAuthors' views not official US Army or DoD policy. Department of Defense Grant W81XWH‐15‐ 2‐0038This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.