The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model.
Shock
; 34(5): 508-16, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20357697
ABSTRACT
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 caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. 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 h, messenger RNA (mRNA) and protein expression of bile salt transporters was determined by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, on in vivo liver biopsies. All resuscitated septic pigs developed a normotensive hyperdynamic circulation with increased portal flow. After 21 h of peritonitis, no signs of biochemical or histological cholestasis were present. Na-taurocholate cotransporting polypeptide and bile salt export pump mRNA were downregulated by 83% (P = 0.001) and 67% (P = 0.001), respectively, in comparison with controls, whereas multidrug resistance-associated protein 4 (MRP4) mRNA was upregulated by 85% (P = 0.02). Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peritonite
/
Ressuscitação
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Ácidos e Sais Biliares
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Norepinefrina
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Derivados de Hidroxietil Amido
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Sepse
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Transportadores de Cassetes de Ligação de ATP
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Transportadores de Ânions Orgânicos Dependentes de Sódio
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Simportadores
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Shock
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Bélgica