Sex-dependent responses to exertional heat stroke in mice

Abstract

With increasing participation of females in endurance athletics and active military service, it is important to determine if there are inherent sex-dependent susceptibilities to exertional heat injury or heat stroke. In this study we compared responses of male and female adult mice to exertional heat stroke (EHS). All mice were instrumented for telemetry core temperature measurements and were exercise-trained for 3 wk before EHS. During EHS, environmental temperature was 37.5°C (35% RH) while the mice ran on a forced running wheel, using incremental increases in speed. The symptom-limited endpoint was loss of consciousness, occurring at ~42.2°C core temperature. Females ran greater distances (623 vs. 346 m, P < 0.0001), reached faster running speeds (7.2 vs. 5.1 m/min, P < 0.0001), exercised for longer times (177 vs. 124 min, P < 0.0001), and were exposed to greater internal heat loads (240 vs.160°C·min; P < 0.0001). Minimum Tc during hypothermic recovery was ~32.0°C in both sexes. Females lost 9.2% body weight vs. 7.5% in males ( P < 0.001). Females demonstrated higher circulating corticosterone (286 vs 183 ng/ml, P = 0.001, at 3 h), but most plasma cytokines were not different. A component of performance in females could be attributed to greater body surface area/mass and greater external power performance. However, there were significant and independent effects of sex alone and a crossed effect of "sex × power" on performance. These results demonstrate that female mice have greater resistance to EHS during exercise in hyperthermia and that these effects cannot be attributed solely to body size. NEW & NOTEWORTHY Female mice are surprisingly more resistant to exertional heat stroke than male mice. They run faster and longer and can withstand greater internal heat loads. These changes cannot be fully accounted for by increased body surface/mass ratio in females or on differences in aerobic performance. Although the stress-immune response in males and females was similar, females exhibited markedly higher plasma corticosteroid levels, which were sustained over 14 days of recovery.

Delayed metabolic dysfunction in myocardium following exertional heat stroke in mice

“…They greatly outperformed the males in terms of their exercise performance and resistance to hyperthermia, which we previously reported (Garcia et al . 2018), and there were no outward indications of underlying cardiovascular difficulties or health issues during this period. Several potential alternative mechanisms are worthy of consideration.…”

“…2015, 2017; Garcia et al . 2018). Briefly, mice were taken to the lab from the animal facility 24 h prior to the experiment but kept on the same light cycle and in their home cage.…”

“…The pre-clinical model of EHS employed in the current study was previously described in detail (King et al 2015(King et al , 2017Garcia et al 2018). Briefly, mice were taken to the lab from the animal facility 24 h prior to the experiment but kept on the same light cycle and in their home cage.…”

“…Within a few minutes of rest, after being unconscious, they returned to normal resting behaviour. The composite performance data for these male and female mice were reported previously (Garcia et al 2018), but some comparative data for males and females are shown in Table 1 interpretation of metabolomic results. As shown in Table 1, female mice ran ß39% longer in the heat, covered nearly twice the distance, and reached speeds ß40% higher than their male counterparts.…”

“…We studied metabolic biomarkers of changes in cardiac metabolites that could indicate long-term consequences. We also compared metabolomic responses between male and female mice because they have strikingly different exercise responses in the heat (Garcia et al 2018) and exhibit marked differences in their predominant metabolic strategies for energy storage and utilization (Blaak, 2001;Lyons et al 2013;Mauvais-Jarvis, 2015).…”