Cholestatic liver dysfunction frequently occurs during critical illness. Administration of parenteral nutrition (PN) is thought to aggravate this. Underlying mechanisms are not clear.status: publishe

Vanwijngaerden, Yoo-Mee

Langouche, Lies

Derde, Sarah

Liddle, Christopher

Coulter, Sally

Van den Berghe, Greet

Mesotten, Dieter

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State University of New York College at Cortland,

Digital Commons @ Cortland (SUNY College Cortland)

Athletes, Women\u27s Lacrosse

BACKGROUND: Cholestatic liver dysfunction frequently occurs during critical illness. Administration of parenteral nutrition (PN) is thought to aggravate this. Underlying mechanisms are not clear. METHODS: In a burn model of prolonged critical illness, rabbits were randomized to a nutritional strategy either accepting caloric deficits (fasted, n = 11) or covering caloric needs by PN (fed, n = 10). At baseline and after 7 days of critical illness, markers of hepatotoxicity, circulating bile acids, and the hepatobiliary transport system were studied. RESULTS: Fasted animals had lower circulating alanine aminotransferase/aspartate aminotransferase levels than did the fed animals at day 7. Compared with baseline values, fed animals displayed lower serum unconjugated cholic acid (CA) and deoxycholic acid (DCA) levels. Unconjugated DCA remained unaltered in fasted animals. Unconjugated lithocholic acid was increased comparably in all animals, whereas hyodeoxycholic acid was not altered. In contrast, fasting induced a shift from unconjugated CA and DCA to glyco-CA and glyco-DCA. Total bile acids did not correlate with the bile acid-producing enzyme CYP7A1, but with the basolateral efflux transporter MRP3. Fasting increased protein expression of the basolateral (MRP3) and the canalicular (BSEP) transporter, whereas the canalicular efflux pump MRP2 was suppressed. Gene expression levels of the nuclear receptor farnesoid X receptor were lower with fasting and correlated inversely with MRP3. The heterodimer partner of farnesoid X receptor, retinoid X receptor α, was increased with fasting and correlated positively with MRP3. CONCLUSIONS: During prolonged critical illness, withholding PN improved markers for hepatocyte injury and accentuated bile acid transport toward the blood. This suggests that the latter is an adaptive rather than a dysfunctional feedback to illness.status: publishe

van den Berghe, Greet

Lirias

Shock

IMPACT OF PARENTERAL NUTRITION VERSUS FASTING ON HEPATIC BILE ACID PRODUCTION AND TRANSPORT IN A RABBIT MODEL OF PROLONGED CRITICAL ILLNESS

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Yoo-Mee Vanwijngaerden

Lies Langouche

Sarah Derde

Christopher Liddle

Sally Coulter

Greet van den Berghe

Dieter Mesotten

Crossref

Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness

http://pdfs.journals.lww.com/shockjournal/2014/01000/Impact_of_Parenteral_Nutrition_Versus_Fasting_on.7.pdf?token=method|ExpireAbsolute;source|Journals;ttl|1503038651113;payload|mY8D3u1TCCsNvP5E421JYK6N6XICDamxByyYpaNzk7FKjTaa1Yz22MivkHZqjGP4kdS2v0J76WGAnHACH69s21Csk0OpQi3YbjEMdSoz2UhVybFqQxA7lKwSUlA502zQZr96TQRwhVlocEp/sJ586aVbcBFlltKNKo+tbuMfL73hiPqJliudqs17cHeLcLbV/CqjlP3IO0jGHlHQtJWcICDdAyGJMnpi6RlbEJaRheGeh5z5uvqz3FLHgPKVXJzdpGRzmTA0M/Vx2WsqiQOgtbVB5oK4HJMgCWlxgbaIiX9sDGJuGrOCd+xtAkMnZkw6;hash|SLGrwGAT7PVyzQRydbIXaA==

Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness

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Digital Commons @ Cortland (SUNY College Cortland)

Digital Commons @ Cortland (SUNY College Cortland)

Digital Commons @ Cortland (SUNY College Cortland)

Digital Commons @ Cortland (SUNY College Cortland)

Digital Commons @ Cortland (SUNY College Cortland)

Digital Commons @ Cortland (SUNY College Cortland)

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