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Updated: Aug 17, 2026

A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Evidence for endothelial cell activation/injury in heatstroke
A Bouchama1, M M Hammami, A Haq
1Department of Medicine, King Faisai Specialist Hospital and Research Centre, Rlyadh, Saudi Arabia.
Objectives:
We treated the hypothesis that heatstroke is associated with endothelial cell activation/injury and examined the possibility that the markers of endothelial cell activation/injury may be associated with its severity and complications such as disseminated intravascular coagulation, lung injury, and renal dysfunction.
Design:
Prospective analyses.
Setting:
Heatstroke Center in Makkah, Saudi Arabia.
Patients:
Twenty-two adult patients with heatstroke.
Interventions:
The plasma concentration of endothelin, circulating intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor-antigen values were measured, respectively, by radioimmunoassay, enzyme-linked immunosorbent assay, and rocket electroimmunoassay, in heatstroke patients on admission (precooling) and after complete cooling (postcooling), and in ten normal control patients.
Measurements And Main Results:
Precooling heatstroke patients (rectal temperature 40.9 +/- 1.1 [SD] degrees C) had increased circulating concentrations of endothelin, c-ICAM-1, and von Willebrand factor-antigen in 100%, 80%, and 77% of patients to 126.4 +/- 11.2 pmol/L, 523.1 +/- 154.4 ng/mL, and 3.85 +/- 2.3 U/mL, respectively (control values: 13.7 +/- 4.2 pmol/L [p < .001]; 247.4 +/- 68.2 ng/ml [p < .001]; and < 1.5 U/mL, respectively). There was a significant (r2 = .68, p < .01) correlation between circulating ICAM-1 and endothelin concentrations. Plasma endothelin concentration correlated negatively with temperature (r2 = .35, p < .05). Mean endothelin concentration was similar in patients with or without renal dysfunction, and mean von Willebrand factor-antigen concentration was similar in patients with or without lung injury or disseminated intravascular coagulation. There were no significant correlations between circulating ICAM-1, endothelin, or von Willebrand factor-antigen concentration and the Simplified Acute Physiology core. After cooling, mean circulating ICAM-1 and endothelin concentrations decreased significantly to 400 +/- 109 ng/mL and 93 +/- 38.5 pmol/L, respectively, whereas the mean von Willebrand factor-antigen concentration increased to 5.55 +/- 2.18 U/mL (p > .05).
Conclusions:
Our findings of increased circulating concentrations of circulating ICAM-1, endothelin, and von Willebrand factor-antigen are consistent with the hypothesis that heatstroke is associated with endothelial cell activation/injury. Whether the endothelial cell activation/injury is implicated in the pathophysiology of this disorder merits further studies.
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