activated protein c ameliorates coagulopathy but does not influence outcome in lethal h1n1 influenza a controlled laboratory study活化蛋白c改善凝血病但不影响在致命的甲型h1n1流感控制实验室研究结果.pdfVIP

Schouten et al. Critical Care 2010, 14:R65 /content/14/2/R65 R E S E A R C H Open Access Research Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study 1,2 2,3,4 5 5 6 7 Marcel Schouten* , Koenraad F van der Sluijs , Bruce Gerlitz , Brian W Grinnell , Joris JTH Roelofs , Marcel M Levi , 1,2 1,2,7 Cornelis van t Veer and Tom van der Poll Abstract Introduction: Influenza accounts for 5 to 10% of community-acquired pneumonias and is a major cause of mortality. Sterile and bacterial lung injuries are associated with procoagulant and inflammatory derangements in the lungs. Activated protein C (APC) is an anticoagulant with anti-inflammatory properties that exert beneficial effects in models of lung injury. We determined the impact of lethal influenza A (H1N1) infection on systemic and pulmonary coagulation and inflammation, and the effect of recombinant mouse (rm-) APC hereon. Methods: Male C57BL/6 mice were intranasally infected with a lethal dose of a mouse adapted influenza A (H1N1) strain. Treatment with rm-APC (125 μg intraperitoneally every eight hours for a maximum of three days) or vehicle was initiated 24 hours after infection. Mice were euthanized 48 or 96 hours after infection, or observed for up to nine days. Results: Lethal H1N1 influenza resulted in systemic and pulmonary activation of coagulation, as reflected by elevated plasma and lung levels of thrombin-antithrombin complexes and fibrin degradation products. These procoagulant changes were accompanied by inhibition of the fibrinolytic response due to enhanced release o