OBJECTIVE: During peritonitis, intra-abdominal fibrin entraps bacteria and hampers their elimination. Systemic administration of anticoagulant activated protein C improves survival in patients with severe sepsis, but its precise mode of action is unclear. This study in polymicrobial peritonitis assessed the effects of local activated protein C administration in peritoneal lavage fluid on coagulation, fibrinolysis, and survival. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Twenty-four hours after induction of peritonitis by cecal ligation and puncture, mice underwent peritoneal lavage with activated protein C (1.0 microg/mL) or saline. Peritoneal lavage fluid, blood, and lungs were sampled after 24, 48, or 72 hrs (n = 8/group/time point). For survival analysis, maximum observation was 96 hrs (n = 22/group). Clotting time, tissue factor expression, thrombin-antithrombin complexes, fibrin degradation products (D-dimers), plasminogen activator, and plasminogen activator inhibitor were used to assess coagulation and fibrinolysis responses. MEASUREMENTS AND MAIN RESULTS: Activated protein C lavage reduced abdominal bacterial load, abdominal and pulmonary clotting times, D-dimers (p < .05 vs. saline), pulmonary tissue factor expression, and fibrin depositions, without clear effects on systemic thrombin generation. Activated protein C lavage decreased plasma and abdominal tissue plasminogen activator levels with increased inhibitor plasminogen activator inhibitor-1 levels (p < .05) but had reverse effects on pulmonary fibrinolysis. Survival improved from 55% (saline) to 80% after intra-abdominal activated protein C administration (p = .03). CONCLUSIONS: Peritoneal lavage with activated protein C may rebalance coagulation and fibrinolysis within compartments and improve survival in polymicrobial peritonitis.
OBJECTIVE: During peritonitis, intra-abdominal fibrin entraps bacteria and hampers their elimination. Systemic administration of anticoagulant activated protein C improves survival in patients with severe sepsis, but its precise mode of action is unclear. This study in polymicrobial peritonitis assessed the effects of local activated protein C administration in peritoneal lavage fluid on coagulation, fibrinolysis, and survival. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Twenty-four hours after induction of peritonitis by cecal ligation and puncture, mice underwent peritoneal lavage with activated protein C (1.0 microg/mL) or saline. Peritoneal lavage fluid, blood, and lungs were sampled after 24, 48, or 72 hrs (n = 8/group/time point). For survival analysis, maximum observation was 96 hrs (n = 22/group). Clotting time, tissue factor expression, thrombin-antithrombin complexes, fibrin degradation products (D-dimers), plasminogen activator, and plasminogen activator inhibitor were used to assess coagulation and fibrinolysis responses. MEASUREMENTS AND MAIN RESULTS: Activated protein C lavage reduced abdominal bacterial load, abdominal and pulmonary clotting times, D-dimers (p < .05 vs. saline), pulmonary tissue factor expression, and fibrin depositions, without clear effects on systemic thrombin generation. Activated protein C lavage decreased plasma and abdominal tissue plasminogen activator levels with increased inhibitor plasminogen activator inhibitor-1 levels (p < .05) but had reverse effects on pulmonary fibrinolysis. Survival improved from 55% (saline) to 80% after intra-abdominal activated protein C administration (p = .03). CONCLUSIONS: Peritoneal lavage with activated protein C may rebalance coagulation and fibrinolysis within compartments and improve survival in polymicrobial peritonitis.
Authors: Farzad Ebrahimi; Madhu S Malo; Sayeda Nasrin Alam; Angela K Moss; Halim Yammine; Sundaram Ramasamy; Brishti Biswas; Kathryn T Chen; Nur Muhammad; Golam Mostafa; H Shaw Warren; Elizabeth L Hohmann; Richard A Hodin Journal: J Gastrointest Surg Date: 2011-03-01 Impact factor: 3.452
Authors: Diego A Vicente; Matthew J Bradley; Benjamin Bograd; Crystal Leonhardt; Eric A Elster; Thomas A Davis Journal: J Inflamm (Lond) Date: 2018-05-24 Impact factor: 4.981
Authors: Pierre Raeven; Alma Salibasic; Susanne Drechsler; Katrin Maria Weixelbaumer; Mohammad Jafarmadar; Martijn van Griensven; Soheyl Bahrami; Marcin Filip Osuchowski Journal: PLoS One Date: 2013-02-08 Impact factor: 3.240