Objectives: We tested the hypothesis that heatstroke is associated wit
h endothelial cell activation/injury and examined the possibility that
the markers of endothelial cell activation/injury may be associated w
ith its severity and complications such as disseminated intravascular
coagulation, lung injury, and renal dysfunction. Design: Prospective a
nalyses. Setting: Heatstroke Center in Makkah, Saudi Arabia. Patients:
Twenty-two adult patients with heatstroke. Interventions: The plasma
concentration of endothelin, circulating intercellular adhesion molecu
le-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 (p
recooling) and after complete cooling (postcooling), and in ten normal
control patients. Measurements and Main Results: Precooling heatstrok
e patients (rectal temperature 40.9 +/- 1.1 [SD]degrees C) had increas
ed circulating concentrations of endothelin, c-ICAM-1, and von Willebr
and 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 (c
ontrol 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) = .6
8, p<.01) correlation between circulating ICAM-1 and endothelin concen
trations. Plasma endothelin concentration correlated negatively with t
emperature (r(2) = .35, p<.05). Mean endothelin concentration was simi
lar in patients with or without renal dysfunction, and mean von Willeb
rand factor-antigen concentration was similar in patients with or with
out 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-an
tigen concentration increased to 5.55 +/- 2.18 U/mL (p>.05). Conclusio
ns: Our findings of increased circulating concentrations of circulatin
g ICAM-1, endothelin, and von Willebrand factor-antigen are consistent
with the hypothesis that heatstroke is associated with endothelial ce
ll activation/injury. Whether the endothelial cell activation/injury i
s implicated in the pathophysiology of this disorder merits further st
udies.