ObjectivesWe tested 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.DesignProspective analyses.SettingHeatstroke Center in Makkah, Saudi Arabia.PatientsTwenty-two adult patients with heatstroke.InterventionsThe 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 ResultsPrecooling heatstroke patients (rectal temperature 40.9 plus minus 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 plus minus 11.2 pmol/L, 523.1 plus minus 154.4 ng/mL, and 3.85 plus minus 2.3 U/mL, respectively (control values: 13.7 plus minus 4.2 pmol/L [p less than .001]; 247.4 plus minus 68.2 ng/mL [p less than .001]; and less than 1.5 U/mL, respectively). There was a significant (r2equals .68, p less than .01) correlation between circulating ICAM-1 and endothelin concentrations. Plasma endothelin concentration correlated negatively with temperature (r2equals .35, p less than .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 plus minus 109 ng/mL and 93 plus minus 38.5 pmol/L, respectively, whereas the mean von Willebrand factor-antigen concentration increased to 5.55 plus minus 2.18 U/mL (p more than .05).ConclusionsOur 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.(Crit Care Med 1996; 24:1173-1178)