Amino Acid-Based Oral Rehydrat on Solution Mitigates Exertional Heat Stroke Severity but Does Not Alter the Innate Immune Response

Theadverse sequelae following exertional heat stroke (EHS) is hypothesized to be aconsequence of heat cytotoxicity and endotoxin leakage secondary to increasesin gut permeability. Administration ofspecific amino acids has been shown to tighten the mucosal barrier, reduceparacellular permeability, decrease endotoxin leakage, and suppress the subsequentinflammatory response. The primaryobjective of this study was to determine if an amino acid based oralrehydration solution (AA‐ORS) would increase performance in the heat and dampenthe innate immune response following an EHS protocol when compared to a watercontrol (H 2 O). To explorethis, C57 BL/6J mice were implanted with temperature transmitters and underwentfour familiarization sessions. On the evening prior to EHS, mice were gavaged with 150 μl of either the AA‐ORS or H 2 O. The EHS protocol was conducted in an environmental chamber at a temperature of 37.5°C with 30% relative humidity and utilized a forced incremental running protocol. TheEHS protocol continued until neurological symptoms were limiting (core temperature(Tc) 42.2°C ± 0.2 H 2 O and AA‐ORS). Tissue and blood samples were collected at 0.5, 3, and 24 h post EHS. All mice survived until tissue collection. Performance in the heat was similar between groups as determined by percent dehydration, max speed, distance, time to Tc max, and thermal load (P>0.05). The extent of hypothermia during recovery, a marker of EHS severity, was mitigated with AA‐ORS (P=0.0054). Minimum Tc (AA‐ORS:32.9°C ± 0.4; H 2 O: 32.1°C ± 0.8; P=0.0020), hypothermia depth (AA‐ORS: 33.3 ±0.5 min; H 2 O: 32.5 ± 0.8 min; P=0.0024), and hypothermia length (AA‐ORS: 186.9 ± 47.3 min; H 2 O: 243.6 ± 42.3 min; P=0.0017) were all significantly improved by AA‐ORS. Although AA‐ORS reduced paracellular permeability (4 kDa FITC, Ussing chamber) at both the 30 min and 3 h timepoints (P<0.05), it did not affect the cytokine or chemokine profile (25 plex Luminex panel) in response to EHS at any time point (P>0.05). Inflammation in hypothalamus was alsomeasured as an indication of EHS severity. No differences were seen between AA‐ORS and H 2 O in mRNA upregulation of IL‐1β, IL‐6, TNFα, MCP‐1, MIP‐1α, MIP‐1β or pattern recognition receptors TLR‐4 and CD14 at the 0.5 or 3 h time points. Further, corticosterone, a hormone that has been shown to suppress the innate immuneresponse, did not differ between treatment groups at any time point. These results suggest that an AA‐ORS improves Tc regulation during EHS recovery, but this dosage had no effect on the systemic inflammatory response that isc haracteristic of EHS. Author views not official US Army or Do Dpolicy. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .