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 and subsequent organ damage. We assessed the impact of a single EHI bout (EHI0) or 2 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 minutes, 3 hours, 1 day or 7 days after the EHI. We observed that mice undergoing repeated EHI events (EHI1, EHI3, and EHI7) had longer running distances prior to collapse (~ 528 meters), tolerated higher core temperatures (~0.18°C) prior to collapse, and had higher minimum core temperature (indicative of injury severity) during recovery relative to EHI0 group (~2.18°C; all P < .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 & liver HSP70, and lower corticosterone, FABP2, MIP-1β, MIP-2, and IP-10 relative to mice experiencing a single EHI at specific points during the recovery period (typically 30-min to 3-hr after the EHI). Our findings indicate that an EHI event may initiate some adaptive processes that provide acute heat resilience to subsequent EHI conditions. Data and code are available at Open Science Framework repository: https://osf.io/n5ahf/?view_only=bca7ccb1b1554e1192ae776e6a7584d3