EHS ENT EHS H2O P ValueInitial weight (g) 27.8 ± 1.7 27.3 ± 1.4 0.1027

PerformanceDehydration (%) 9.4 ± 2.1 9.3 ± 1.7 0.8177Max speed (m/min) 5.9 ± 1.1 5.8 ± 0.1 0.5742Distance (meters) 707.8 ± 251.5 693.9 ± 180 0.7595

Thermal Area Tc Max (°C) 42.2 ± 0.2 42.2 ± 0.2 0.9673Time to Tc Max (min) 160.9 ± 38.8 155.5 ± 27.7 0.8463Thermal Load 552.5 ± 89.5 545.7 ± 82.7 0.7098Ascending Thermal Area (°C min) 523.7 ± 88.2 519.0 ± 79.8 0.7885Descending Thermal Area (°C min) 26.9 ± 6.3 26.5 ± 5.5 0.7739

Hypothermia Severity#Time to Tc Minimum (min) 129.3 ± 34.6 136.2 ± 39.7 0.6159#Tc Minimum (°C) 32.9 ± 0.4 32.1 ± 0.8 0.0020**#Hypothermia depth (°C) 33.3 ± 0.5 32.5 ± 0.8 0.0024**#Hypothermia length (min) 186.9 ± 47.3 243.6 ± 42.3 0.0017**

METHODS

INTRODUCTION

1King M.A., 1Dineen S.M., 1Ward J.A., 1Mayer T.A., 1Plamper M.L., 2Grosche A., 2XiaoDong Xu, 2Sasidharan A., 1Ward M.D., 3Clanton T.L., 2Vidyasagar S., 1L.R. Leon1US Army Research Institute of Environmental Medicine, Thermal & Mountain Medicine Division, Natick, Massachusetts 01760

2University of Florida, Radiation Oncology, Gainesville, FL 32611;3University of Florida, College of Health and Human Performance, Gainesville, FL 32611

RESULTS

CONCLUSIONS

• The adverse sequelae following exertional heat stroke (EHS) is hypothesized to be a consequence of endotoxin leakage secondary to increases in gut permeability.

• Oral administration of specific amino acids have been shown to tighten the mucosal barrier, reduce paracellular permeability, decrease endotoxin leakage, and suppress the inflammatory response during a variety of stressors.

• We hypothesized that Enterade® (ENT), an amino acid based oral rehydration solution, will protect the gut from increased permeability during EHS, mitigating the systemic inflammatory response.

• The purpose of this study was to determine if ENT can:

1. Increase performance in the heat

2. Reduce paracellular permeability

3. Suppress the systemic inflammatory response

4. Increase cell proliferation and accelerate recovery

Study Design

Thermoregulatory Performance Small Intestine Histology

Implant Temperature Transmitters

Free Running Wheels Added

Familiarization Sessions (x4)

Randomization

EHS Protocol Exercise Control

ENT or H2O ENT or H2O

EHS Protocol Gut Permeability

Data are presented as mean ± SD. Time points were combined for treatment groups EHS ENT (n= 48) EHS H2O (n= 46)(#) which includes only the 24 hr group; EHS ENT (n=15) EHS H2O (n=15). **P<0.005;

ENT decreases EHS severity as indicated by depth and duration of hypothermia

ENT mitigates increases in gut permeability

37.5°C / 30% RH

• ENT attenuates minimum Tc reached, hypothermia depth, and hypothermia length.

• ENT decreases paracellular permeability as evidenced by conductance, FITC dextran, and histology.

• Circulating markers of organ injury and the innate immune response were similar between ENT and H2O throughout the course of recovery.

• These results suggest that ENT improves Tc regulation during EHS recovery, but this dosage had no effect on the systemic inflammatory response that is characteristic of EHS at select time points.

Author views not official US Army or DoD policy.

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

EHS ENT vs. H2O

**P=0.0054

*P<0.05

30m 3h 24hNC

H2O H2O H2O H2OENT ENT ENT ENT

Circulating BiomarkersSimilar Innate Immune Response & Organ Damage

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ENT Preserves Villi Height and Width

**C57/Bl6 mice

FITC-Dextran Conductance Current