Impact of successive exertional heat injuries on thermoregulatory and systemic inflammatory responses in mice

The purpose of the study was to determine if repeated exertional heat injuries (EHIs) worsen the inflammatory response. We assessed the impact of a single EHI bout (EHI0) or two separate EHI episodes separated by 1 (EHI1), 3 (EHI3), and 7 (EHI7) days in male C57BL/6J mice (n = 236). To induce EHI, mice underwent a forced running protocol until loss of consciousness or core temperature reached ≥ 42.7°C. Blood and tissue samples were obtained 30 min, 3 h, 1 day, or 7 days after the EHI. We observed that mice undergoing repeated EHI (EHI1, EHI3, and EHI7) had longer running distances before collapse (∼528 m), tolerated higher core temperatures (∼0.18°C higher) before collapse, and had higher minimum core temperature (indicative of injury severity) during recovery relative to EHI0 group (∼2.18°C higher; all P < 0.05). Heat resilience was most pronounced when latency was shortest between EHI episodes (i.e., thermal load and running duration highest in EHI1), suggesting the response diminishes with longer recoveries between EHI events. Furthermore, mice experiencing a second EHI exhibited increased serum and liver HSP70, and lower corticosterone, FABP2, MIP-1β, MIP-2, and IP-10 relative to mice experiencing a single EHI typically at 30 min to 3 h after EHI. Our findings indicate that an EHI event may initiate some adaptive processes that provide acute heat resilience to subsequent EHI conditions. NEW & NOTEWORTHY Mice undergoing repeated exertional heat injuries, within 1 wk of an initial heat injury, appear to have some protective adaptations. During the second exertional heat injury, mice were able to run longer and sustain higher body temperatures before collapse. Despite this, the mice undergoing a second exertional heat injury were more resilient to the heat as evidenced by attenuated minimum body temperature, higher HPS70 (serum and liver), lower corticosterone, and lower FABP2.