Recombinant Activated Protein C Attenuates Endothelial Injury and Inhibits Procoagulant Microparticles Release in Baboon Heatstroke
| Autor: | Dominique de Prost, Mohammed Dehbi, Abderrezak Bouchama, Abdelmoneim Eldali, Jean Marie Freyssinet, Fatiha Zobairi, Aaron Kwaasi, Corinne Kunzelmann |
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| Rok vydání: | 2008 |
| Předmět: |
Time Factors
Heat Stroke Multiple Organ Failure Thrombomodulin medicine.medical_treatment Antithrombin III Pharmacology Severity of Illness Index Tissue plasminogen activator Fibrin Fibrin Fibrinogen Degradation Products Fibrinolytic Agents Fibrinolysis medicine Animals Humans Infusions Intravenous Transport Vesicles Blood Coagulation biology Interleukin-6 business.industry Heatstroke medicine.disease Recombinant Proteins Disease Models Animal Cytoprotection Tissue Plasminogen Activator Immunology biology.protein Papio hamadryas Endothelium Vascular Cardiology and Cardiovascular Medicine Cell activation business Protein C Fibrinolytic agent Peptide Hydrolases medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 28:1318-1325 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.107.161737 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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