Title: The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model
Authors: Wauters, Joost ×
Mesotten, Dieter
Van Zwam, Kenny
van Pelt, Jos
Thiessen, Steven
Dieudonné, Anne-Sophie
Vanderborght, Sara
Van den Berghe, Greet
Wilmer, Alexander #
Issue Date: Nov-2010
Publisher: BioMedical Press
Series Title: Shock vol:34 issue:5 pages:508-516
Abstract: INTRODUCTION:: Sepsis is often associated with cholestatic liver dysfunction, caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models the role of ischemic hepatitis due to liver hypoperfusion cannot be delineated. We hypothesized that, hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. METHODS:: Fifteen anesthetized and instrumented pigs were randomized to either fecal peritonitis (n=8) or control (n=7). Resuscitation was performed by hydroxyethyl starch and norepinephrine infusion. Hemodynamic parameters and markers of cholestatic and ischemic hepatic dysfunction were recorded. At baseline and after 21 hours, mRNA and protein expression of bile salt transporters was determined by respectively quantitative RT-PCR and immunohistochemistry on in vivo liver biopsies. RESULTS:: All resuscitated septic pigs developed a normotensive, hyperdynamic circulation with increased portal flow. After 21h of peritonitis, no signs of biochemical or histological cholestasis were present. Na-taurocholate co-transporting polypeptide (NTCP) and bile salt export pump (BSEP) mRNA were downregulated by respectively 83% (p=0.001) and 67% (p=0.001) in comparison with controls, while multidrug resistance-associated protein 4 (MRP4) mRNA was upregulated by 85% (p=0.02). BSEP and MRP2 staining was downregulated in septic pigs. CONCLUSIONS:: During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (NTCP) and canalicular efflux (BSEP) of bile salts were downregulated without hemodynamical signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids.
ISSN: 1073-2322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hepatology
Laboratory of Intensive Care Medicine
Section Woman - Miscellaneous (-)
Laboratory for Clinical Infectious and Inflammatory Disorders
Gynaecological Oncology
× corresponding author
# (joint) last author

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