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Updated: Mar 9, 2026

A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Plasma hyperosmolality improves tolerance to combined heat stress and central hypovolemia in humans
Daniel Gagnon1,2,3, Steven A Romero1, Hai Ngo1
1Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas and University of Texas Southwestern Medical Center, Dallas, Texas.
Abstract:
Heat stress profoundly impairs tolerance to central hypovolemia in humans via a number of mechanisms including heat-induced hypovolemia. However, heat stress also elevates plasma osmolality; the effects of which on tolerance to central hypovolemia remain unknown. This study examined the effect of plasma hyperosmolality on tolerance to central hypovolemia in heat-stressed humans. With the use of a counterbalanced and crossover design, 12 subjects (1 female) received intravenous infusion of either 0.9% iso-osmotic (ISO) or 3.0% hyperosmotic (HYPER) saline. Subjects were subsequently heated until core temperature increased ~1.4°C, after which all subjects underwent progressive lower-body negative pressure (LBNP) to presyncope. Plasma hyperosmolality improved LBNP tolerance (ISO: 288 ± 193 vs.
Hyper:
382 ± 145 mmHg × min, P = 0.04). However, no differences in mean arterial pressure (P = 0.10), heart rate (P = 0.09), or muscle sympathetic nerve activity (P = 0.60, n = 6) were observed between conditions. When individual data were assessed, LBNP tolerance improved ≥25% in eight subjects but remained unchanged in the remaining four subjects. In subjects who exhibited improved LBNP tolerance, plasma hyperosmolality resulted in elevated mean arterial pressure (ISO: 62 ± 10 vs.
Hyper:
72 ± 9 mmHg, P < 0.01) and a greater increase in heart rate (ISO: +12 ± 24 vs. HYPER: +23 ± 17 beats/min, P = 0.05) before presyncope. No differences in these variables were observed between conditions in subjects that did not improve LBNP tolerance (all P ≥ 0.55). These results suggest that plasma hyperosmolality improves tolerance to central hypovolemia during heat stress in most, but not all, individuals.
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