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Cholestasis enhances liver ischemia/reperfusion‐induced coagulation activation in rats
Author(s) -
Kloek Jaap J.,
Levi Marcel,
Heger Michal,
Van Der Loos Chris M.,
Gouma Dirk J.,
Van Gulik Thomas M.
Publication year - 2010
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2009.00579.x
Subject(s) - cholestasis , medicine , antithrombin , ischemia , plasminogen activator , reperfusion injury , prothrombin time , endocrinology , liver injury , gastroenterology , partial thromboplastin time , platelet , heparin
Aim: Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods: Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results: Plasma AST and ALT levels were higher after I/R in cholestatic rats ( P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion ( P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion ( P < 0.05). I/R in cholestatic rats resulted in a 12‐fold vs. 7‐fold ( P < 0.01) increase in markers for thrombin generation and a 6‐fold vs. 2‐fold ( P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI‐1) during reperfusion. Conclusions: Cholestasis significantly enhances I/R‐induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis.