title: A virtual rat for simulating environmental and exertional heat stress.
abstract: Severe cases of environmental or exertional heat stress can lead to varying degrees of organ dysfunction. To understand heat-injury progression and develop efficient management and mitigation strategies, it is critical to determine the thermal response in susceptible organs under different heat-stress conditions. To this end, we used our previously published virtual rat, which is capable of computing the spatiotemporal temperature distribution in the animal, and extended it to simulate various heat-stress scenarios, including 1) different environmental conditions, 2) exertional heat stress, 3) circadian rhythm effect on the thermal response, and 4) whole body cooling. Our predictions were consistent with published in vivo temperature measurements for all cases, validating our simulations. We observed a differential thermal response in the organs, with the liver experiencing the highest temperatures for all environmental and exertional heat-stress cases. For every 3°C rise in the external temperature from 40 to 46°C, core and organ temperatures increased by ∼0.8°C. Core temperatures increased by 2.6 and 4.1°C for increases in exercise intensity from rest to 75 and 100% of maximal O2 consumption, respectively. We also found differences as large as 0.8°C in organ temperatures for the same heat stress induced at different times during the day. Even after whole body cooling at a relatively low external temperature (1°C for 20 min), average organ temperatures were still elevated by 2.3 to 2.5°C compared with normothermia. These results can be used to optimize experimental protocol designs, reduce the amount of animal experimentation, and design and test improved heat-stress prevention and management strategies.
authors.affiliation: Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, United States Army Medical Research and Materiel Command, Fort Detrick, Maryland; and.
authors.forename: Vineet
authors.initials: V
authors.lastname: Rakesh
authors.affiliation: Environmental Health Program, United States Army Center for Environmental Health Research, Fort Detrick, Maryland.
authors.forename: Jonathan D
authors.identifier: http://orcid.org/0000-0002-6430-5888
authors.initials: JD
authors.lastname: Stallings
authors.affiliation: Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, United States Army Medical Research and Materiel Command, Fort Detrick, Maryland; and jaques.reifman.civ@mail.mil.
authors.forename: Jaques
authors.initials: J
authors.lastname: Reifman
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D003198:Computer Simulation; D018882:Heat Stress Disorders / Q000628:therapy; D006358:Hot Temperature; D008297:Male; D008954:Models, Biological; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological
keywords: core temperature circadian rhythm; heat transfer; organ-specific response; three-dimensional computational rat model; whole body cooling