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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1130.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Microvascular Injury, Thrombosis, Inflammation, and Apoptosis in the Pathogenesis of Heatstroke

A Study in Baboon Model

George T. Roberts; Hazem Ghebeh; Muhammad A. Chishti; Falah Al-Mohanna; Rafaat El-Sayed; Futwan Al-Mohanna; Abderrezak Bouchama

From the Departments of Pathology & Laboratory Medicine (G.T.R.), Stem Cell Therapy Research Program (H.G.), Comparative Medicine (M.A.C., F.A., R.E., A.B.), and Biological and Medical Research (F.A.), King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

Correspondence to Abderrezak Bouchama, MD, Department of Comparative Medicine (MBC03), King Faisal Specialist Hospital & Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia. E-mail abouchama{at}kfshrc.edu.sa

Abstract

Objective— Severe heatstroke is a leading cause of morbidity and mortality during heat waves. The pathogenesis of tissue injury, organ failure, and death in heatstroke is not well understood.

Methods and Result— We investigated the pathways of heatstroke-induced tissue injury and cell death in anesthetized baboons (Papio hamadyras) subjected to environmental heat stress until core temperature attained 42.5°C (moderate heatstroke; n=3) or onset of severe heatstroke (n=4) signaled by a fall in systolic blood pressure to <90 mm Hg and rise in core temperature to 43.1±0.1°C. Three sham-heated animals served as controls. Light and electron microscopy revealed widespread hemorrhage and thrombosis, transmural migration of leukocytes, and microvascular endothelium injury in severe heatstroke. Immunohistology and ultrastructural analysis demonstrated increased staining of endothelial von Willebrand factor (vWF), tissue factor (TF), and endothelial leukocyte-platelet interaction. Extensive apoptosis was noted in spleen, gut, and lung, and in hematopoeitic cells populating these organs. Double-labeling studies colocalized active caspase-3 and TF with apoptotic cells. Findings in sham-heated animals were unremarkable.

Conclusion— These data suggested that microvascular injury, thrombosis, inflammation, and apoptosis may play an important role in the pathogenesis of heatstroke injury.

Severe heatstroke is a leading cause of morbidity and mortality during heat waves. The pathogenesis of tissue injury and death in heatstroke is not well understood. Using a heatstroke baboon model, we showed that microvascular injury, thrombosis, inflammation, and apoptosis may play an important pathogenic role.

Key Words: heatstroke • inflammation • apoptosis • endothelium • thrombosis