• Abderrezak Bouchama, Corinne Kunzelmann, Mohammed Dehbi, Aaron Kwaasi, Abdelmoneim Eldali, Fatiha Zobairi, Jean-Marie Freyssinet, and Dominique de Prost.
• Department of Comparative Medicine (MBC03), King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. abouchama@kfshrc.edu.sa
• Arterioscler. Thromb. Vasc. Biol. 2008 Jul 1;28(7):1318-25.

ObjectiveWe tested the hypothesis that the antithrombotic and cytoprotective effects of recombinant human activated protein C (rhAPC) protect baboons against the lethal effects of heatstroke.Methods And ResultsFourteen anesthetized baboons assigned randomly to rhAPC (n=7) or control group (n=7) were heat-stressed in a prewarmed incubator at 44 to 47 degrees C until systolic blood pressure fell below 90 mm Hg, which signaled severe heatstroke. rhAPC was administered intravenously (24 microg/kg/h) for 12 hours at onset of heatstroke. Heat stress induced coagulation and fibrinolysis activation as evidenced by a significant increase from baseline levels in plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator, and D-dimer. Heat stress elicited cell activation/injury as assessed by the release of interleukin (IL)-6, soluble thrombomodulin, and procoagulant microparticles (MPs). rhAPC did not significantly reduce heatstroke-induced thrombin generation, and D-dimer and had no effect on fibrinolytic activity. In contrast, rhAPC infusion attenuated significantly the plasma rise of IL-6 and inhibited the release of soluble thrombomodulin and MPs as compared with control group. No difference in survival was observed between rhAPC-treated and control group.ConclusionsrhAPC given to heatstroke baboons provided cytoprotection, but had no effect on heatstroke-induced coagulation activation and fibrin formation. Inhibition of MPs by rhAPC suggested a novel mechanism of action for this protein.

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