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.
Prospective, randomized study.
University-based research laboratory.
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.
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).
Peritoneal lavage with activated protein C may rebalance coagulation and fibrinolysis within compartments and improve survival in polymicrobial peritonitis.
"*P b 0.05 vs. 0 h. e243 P. Raeven et al. / Thrombosis Research 129 (2012) e238–e245 Author's personal copy post-CLP), but these changes were likely influenced by lavage . Additionally, the latter study assessed only the active circulating PAI-1, and active PAI-1 is prone to serious measurement/handling errors due to its instability (in contrast to total PAI-1) . "
[Show abstract][Hide abstract] ABSTRACT: Plasminogen activator inhibitor type 1 (PAI-1) co-induces septic coagulopathy. We aimed to characterize spatiotemporal PAI-1 gene/protein changes occurring in acute sepsis and tested whether PAI-1 fluctuations correlate with sepsis severity and early outcome.
Female mice underwent cecal ligation and puncture (CLP) in three experiments. I: mild (23 G needle) CLP to compare circulating PAI-1 to its organ gene expression within 0-24h. II: mild or severe (17 G) CLP to asses differences in PAI-1 organ-specific expression and in coagulation/fibrinolysis. III: moderate (18 G) CLP to characterize circulating PAI-1 in survivors (SUR), and to retrospectively compare it to dying (DIE) mice.
In mild sepsis, the trajectory of circulating PAI-1 (1089 ng/ml peak at 24h) was identical to PAI-1 gene expression in the left cranial vena cava (LCVC; 39-fold peak at 24h). PAI-1 expression rise was immediate (60-fold at 6h) and sustained in the liver, but marginal in the kidney, lungs and heart. Body temperature decrease correlated with the PAI-1 expression increase in the liver (rho = -0.79), and blood (protein, rho = -0.53). Regardless of severity, PAI-1 gene expression remained unaltered except the LCVC where it was >3-fold higher in 17G (vs. 23 G). Severe sepsis extended activated partial thromboplastin/pro-thrombin time and increased circulating PAI-1, while antithrombin and fibrinogen decreased at 6 and/or 24h (vs. 23 G). Within 24h of death, circulating PAI-1 in DIE was >3-fold higher versus SUR.
Polymicrobial sepsis caused a gradual circulating PAI-1 release and highly variable gene expression response pattern in organs. Only circulating PAI-1 and PAI-1 expression in the LCVC correlated with response severity and/or outcome.
Thrombosis Research 02/2012; 129(5):e238-45. DOI:10.1016/j.thromres.2012.02.004 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new approach to analyze directional couplers of arbitrary cross section is presented. The ultimate objective is to obtain accurate coupling coefficients for various coupler parameters and to establish the optimal conditions for practical applications of polarization-preserving fiber-optic couplers (PFDCs). The even and odd super-modes for each polarization are obtained using a recently developed Yee's mesh finite-difference vectorial-beam-propagation method (YMFD-VBPM). Subsequently, the coupling coefficient for each polarization is then obtained
[Show abstract][Hide abstract] ABSTRACT: Histochemical and immunohistochemical techniques have been used to detect fibrin deposits in different tissues in humans and experimental animal models with disseminated intravascular coagulation (DIC). Fibrin deposits also have been observed in horses with severe ischemic and inflammatory disorders by histochemical stainings (phosphotungstic acid hematoxylin [PTAH]).
Immunohistochemical (IHC) methods can be used to accurately detect fibrin deposits in horses at risk of DIC.
Tissue-organ samples collected on postmortem examination from 87 horses with severe inflammatory and ischemic gastrointestinal disorders. In addition, tissue samples from 13 horses with colic and colonic obstructions or displacements and from 13 slaughter horses were used as controls.
Tissue samples (kidney, lung, and liver) were stained with PTAH and IHC for blinded histologic examination and comparison. A fibrin score (grades 0 to 4) was established for each tissue sample and for each horse for both techniques.
When the IHC method was used, fibrin deposition was observed in 47.1% of the horses with colic with a poor prognosis, compared with 41.4% with PTAH. An agreement of 70% was achieved when both methods were compared, and the lung was confirmed as the most affected organ. Almost none of the colic and slaughter control horses had fibrin deposits in their tissues.
IHC technique for fibrin antigens was very effective in the detection and identification of fibrin deposits in equine tissues and may be a reliable technique for the postmortem diagnosis of DIC.
Journal of Veterinary Internal Medicine 09/2007; 21(5):1083-9. DOI:10.1111/j.1939-1676.2007.tb03068.x · 1.88 Impact Factor
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