Prior Vancomycin Treatment Mitigates Coagulation and Death in a Severe Exertional Heat Stroke Mouse ModelPrior Vancomycin treatment mitigates coagulation and death in a severe Exertional Heat Stroke mouse model
Authors: Ward Jermaine A. , Ward Shauna M. , Plamper Mark L. , Henderson Chloe G. , Mayer Thomas A. , Leon Lisa R. , Oki Kentaro 
Published: May 2022

During exercise, intestinal leakage of lipopolysaccharide (LPS or endotoxin: a component in the cell walls of Gram‐negative bacteria) into circulation is hypothesized to accelerate exertional heat stroke (EHS) onset and/or increase EHS severity. Conceptually, decreasing intestinal microbe populations via antibiotic treatment could counteract EHS. Accordingly, we determined whether prior treatment with the antibiotic Vancomycin would delay EHS onset and/or mitigate EHS severity and mortality rates using a recently developed mouse model of severe EHS that more accurately recapitulates the human condition. Using a 2X2 treatment design, mice were 1) designated as EHS or Exercise Control (ExC) specimens and 2) given 7 days of Vancomycin or untreated water. Mice were placed in a forced‐running wheel that gradually increased from low‐to‐moderate speed (3.0 to 8.5 m/min, increasing 0.5 m/min every 10 minutes). Ambient temperature was set at 25°C for ExC and 37.5°C for EHS specimens while humidity was set at 30‐70% for all conditions. Treated and untreated EHS mice ran in the wheels until losing consciousness. Each EHS mouse and a conscious, similarly treated ExC counterpart were left undisturbed in their respective chambers for an additional 20 minutes before being sacrificed immediately (0h) or returned to their home cage (25°C) and sacrificed after 3 hours (3h) or 24 hours (24h). Across all timepoints, mortality was higher in untreated (14/63) vs. Vancomycin‐treated (6/47) EHS mice, and percentage of dehydration was attenuated in Vancomycin‐treated vs. untreated EHS mice. Core body temperatures (Tc) and thermal load of Vancomycin EHS mice were lower than untreated EHS mice at the time of heat collapse despite both groups running over comparable times and distances. At 24 hours following the exercise/heat bout, student’s T‐tests indicated that serum alanine aminotransferase (ALT) in untreated EHS is greater than levels in Vancomycin EHS mice, indicating accelerated hepatic recovery with antibiotic treatment. Our working hypothesis is that Vancomycin treatment decreased intestinal bacteria populations, leading to decreased microbial release into circulation and protecting other organs (e.g., liver) from detrimental effects of bacteremia. Consequently, Vancomycin mitigated EHS phenotype in treated mice compared to what was observed in untreated EHS mice.

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