Evidence for endothelial cell activation/injury in heatstroke

Objectives: We 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. 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 (r(2) = .68, p<.01) correlation between circulating ICAM-1 and endothelin concentrations. Plasma endothelin concentration correlated negatively with temperature (r(2) = .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.