Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, the Netherlands.
Shock. 2011 Oct;36(4):417-23. doi: 10.1097/SHK.0b013e31822bcef0.
Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia. Inhibitors of coagulation could exert lung-protective effects via anticoagulant (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could also affect host defense. In this randomized controlled in vivo laboratory study, rats were challenged intratracheally with Pseudomonas aeruginosa, inducing pneumonia, and randomized to local treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin, or danaparoid. Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-AT complexes and fibrin degradation products and decreased pulmonary levels plasminogen activator activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of thrombin-AT complexes increased, and systemic levels of plasminogen activator activity decreased. Although rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. Nebulization of rh-APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial clearance or inflammation, in a rat model of P. aeruginosa pneumonia.
肺泡纤维蛋白周转率紊乱是肺炎的一个特征。凝血抑制剂可通过抗凝（抑制纤维蛋白沉积）和可能的抗炎途径发挥肺保护作用，但也可能影响宿主防御。在这项随机对照的体内实验室研究中，大鼠通过气管内接种铜绿假单胞菌来引发肺炎，并随机接受生理盐水（安慰剂）、重组人活化蛋白 C（rhAPC）、血浆源性抗凝血酶 (AT)、肝素或达那肝素局部治疗。铜绿假单胞菌肺炎诱导了肺内凝血的激活和肺纤维蛋白溶解的抑制，反映在肺内凝血酶-AT 复合物和纤维蛋白降解产物的水平增加以及纤溶酶原激活物活性的降低。铜绿假单胞菌肺炎伴有全身凝血障碍，因为全身凝血酶-AT 复合物的水平增加，而全身纤溶酶原激活物活性降低。尽管 rhAPC 和血浆源性 AT 能有效地限制肺内凝血，但肝素和达那肝素均未影响肺内纤维蛋白的净周转率。重组人 APC 也表现出全身抗凝作用。抗凝治疗既不影响细菌清除率，也不影响肺部炎症。rhAPC 或血浆源性 AT 的雾化吸入可减轻铜绿假单胞菌肺炎大鼠的肺内凝血，但不影响细菌清除率或炎症。
