tailieunhanh - Báo cáo y học: "Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study. | Schouten et al. Critical Care 2010 14 R65 http content 14 2 R65 c CRITICAL CARE RESEARCH Open Access Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza a controlled laboratory study Marcel Schouten 1 2 Koenraad F van der Sluijs2 3 4 Bruce Gerlitz5 Brian W Grinnell5 JorisJTH Roelofs6 Marcel M Levi7 Cornells van t Veer1 2 and Tom van der Poll1 2 7 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 pg 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 of plasminogen activator inhibitor type-1. Rm-APC strongly inhibited coagulation activation in both plasma and lungs and partially reversed the inhibition of fibrinolysis. Rm-APC temporarily reduced pulmonary viral loads but did not impact on lung inflammation or survival. Conclusions Lethal influenza induces procoagulant and antifibrinolytic changes in the lung which can be partially .