title: Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury.
abstract: BACKGROUND
  Sepsis induced acute lung injury (ALI) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALI.
  
  
  METHODS
  Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n = 7 in each group). After a tracheotomy had been performed, ALI was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 microg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% oxygen. Bovine APC (25 microg x kg(-1) x h(-1)) was intravenously administered. The infusion was initiated half an hour post-injury and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution.
  
  
  RESULTS
  In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68 +/- 0.06) ng/ml, vs APC group of (0.62 +/- 0.07) ng/ml at 6 hours, P < 0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32 +/- 0.03) microg/ml at 2 hours, (2.24 +/- 0.06) microg/ml at 4 hours and (2.21 +/- 0.09) microg/ml at 6 hours, vs APC group (2.46 +/- 0.04) microg/ml at 2 hours, (2.40 +/- 0.05) microg/ml at 4 hours and (2.39 +/- 0.07) microg/ml at 6 hours, P < 0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAI-1) both in plasma (control group was (0.68 +/- 0.12) ng/ml at 1 hour, (0.84 +/- 0.06) ng/ml at 2 hours, (0.87 +/- 0.08) ng/ml at 4 hours and (0.91 +/- 0.05) ng/ml at 6 hours, vs APC group (0.42 +/- 0.16) ng/ml at 1 hour, (0.43 +/- 0.04) ng/ml at 2 hours, (0.45 +/- 0.09) ng/ml at 4 hours and (0.45 +/- 0.14) ng/ml at 6 hours, P < 0.01) and in bronchoalveolar lavage fluid (at 6 hours: sham, (1.05 +/- 0.05) ng/ml; control, (1.13 +/- 0.06) ng/ml; APC, (1.06 +/- 0.06) ng/ml; P < 0.05). However, APC failed to prevent the decrease in PaO(2)/FiO(2) ratio. APC-treated rabbits showed no significant difference in platelet count and antithrombin but exhibited less D-dimer production than did the controls. Moreover, APC limited the histopathological score of lung injury (2.6 +/- 0.8 in control, vs 1.4 +/- 0.6 in APC group, P < 0.01).
  
  
  CONCLUSIONS
  Anti-coagulation and pro-fibrinolysis activity may be two of the possible mechanisms by which activated protein C attenuated endotoxin-induced ALI.
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital Capital Medical University, Beijing 100020, China.
authors.forename: Hang-yong
authors.initials: HY
authors.lastname: He
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Bao-sen
authors.initials: BS
authors.lastname: Pang
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000494:pharmacology*; D017293:Protein S / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D018180:Thrombomodulin / Q000097:blood
chemical_list: D004731:Endotoxins; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D017293:Protein S; D018180:Thrombomodulin; D000990:Antithrombin III