Recombinant activated protein c attenuates endothelial injury and inhibits procoagulant microparticles release in baboon heatstroke

Abderrezak Bouchama, Corinne Kunzelmann, Mohammed Dehbi, Aaron Kwaasi, Abdelmoneim Eldali, Fatiha Zobairi, Jean Marie Freyssinet, Dominique De Prost

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objectives - We 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 Results - Fourteen anesthetized baboons assigned randomly to rhAPC (n=7) or control group (n=7) were heat-stressed in a prewarmed incubator at 44 to 47°C until systolic blood pressure fell below 90 mm Hg, which signaled severe heatstroke. rhAPC was administered intravenously (24 μg/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. Conclusions - rhAPC 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.

Original languageEnglish
Pages (from-to)1318-1325
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number7
DOIs
Publication statusPublished - 1 Jul 2008
Externally publishedYes

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Keywords

  • APC
  • Heatstroke
  • Hyperthermia
  • Inflammation
  • Primates
  • Procoagulant microparticles

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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