Decrease in Regeneration Capacity of Rat Liver after External Biliary Drainage

Iyomasa, Shinsuke; Terasaki, Masaki; Kuriki, Hiroshi; Nimura, Yuji; Shionoya, Shigehiko; Kojima, Kensuke; Yoshida, Setsuro

doi:10.1159/000129215

Cited by 33 publications

(36 citation statements)

References 18 publications

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“…Recently, devazepide infusion was described to exert trophic effects on the intact rat liver [14]. This was assumed to be related to cholestasis as devazepide has been shown to decrease bile secretion and bile acid output [29], and cholestasis has induced trophic effects on the liver and biliary tract [15][16][17]. Our present results confirm this hypothesis.…”

Section: Discussionsupporting

confidence: 84%

“…Endogenous hyperCCKemia evoked in the rat by pancreaticobiliary diversion [10][11][12] or biliodigestive shunt [13] did neither influence the intact liver nor liver regeneration. Continuous infusion of CCK-8S did not exert any overt effect on the liver, whereas infusion of the CCK-A receptor antagonist devazepide induced an increased cell proliferation of both hepatocytes and bile duct epithelium in the rat [14], tentatively by a reduced bile flow [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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An Evaluation of the Influence of Devazepide and CCK-8S on the Intact and Resected Rat Liver

Ohlsson

Rehfeld²,

Axelson³

1998

Eur Surg Res

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Background: Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection. Methods: In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the contents of protein, DNA and water and incorporation of tritiated thymidine were measured. Results: Intermittent injections of devazepide increased the liver protein content after 36 h, followed by a decrease after 7 days. The weight, DNA content or cell proliferation was not affected. Two days after liver resection hyperCCKemia was evoked, which was less prominent after 7 days. Devazepide lowered the plasma concentration of CCK, while the infusion of CCK-8S resulted in extremely high concentrations at both time points. The DNA synthesis measured by thymidine incorporation was increased by devazepide on day 2, whereas the weight or protein and DNA contents of the liver were not influenced. CCK-8S infusion decreased the body and liver weight throughout the study, and the protein and DNA contents after 7 days. Conclusions: Intermittent devazepide treatment did not affect the intact liver. Devazepide increased the DNA synthesis 2 days after liver resection but was without other influences on the liver regeneration. CCK-8S induced decreased body weight with ensuing negative effects on the liver regeneration. Neither devazepide nor CCK seem to be of any therapeutic use after liver resection or liver failure.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

An Evaluation of the Influence of Devazepide and CCK-8S on the Intact and Resected Rat Liver

Ohlsson

Rehfeld²,

Axelson³

1998

Eur Surg Res

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“…The present study as well as the recent work [32] has proven that the external biliary drainage could not restore the impaired liver regeneration under obstructive jaundice. Pitt et al [2] showed insignificant effect of biliary decompression on the morbidity and mortality of patients with obstructive jaundice in a prospective randomized trial.…”

Section: Discussionsupporting

confidence: 38%

Differences in Biliary Lipid Excretion after Major Hepatectomy in Obstructive Jaundiced Rats with Preoperative Internal, External, or No Biliary Drainage

Mizuta¹,

Chijiiwa²,

Saiki³

et al. 2002

Eur Surg Res

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Necessity of preoperative biliary drainage for patients with obstructive jaundice is still controversial. We recently reported that liver regeneration after major hepatectomy was better restored in a rat model of obstructive jaundice with preoperative internal biliary drainage than that without biliary drainage or with external biliary drainage. The aim of this study was to investigate the differences in biliary lipid excretion after hepatectomy in obstructive jaundiced rats with or without preoperative internal or external biliary drainage. After bile duct ligation for 7 days, rats were randomly divided into the three groups; obstructive jaundice-hepatectomy (OJ-Hx), internal biliary drainage-hepatectomy (ID-Hx), and external biliary drainage-hepatectomy (ED-Hx) groups. 70% hepatectomy and internal biliary drainage were carried out 7 days after biliary decompression in the latter two groups and without biliary decompression in the OJ-Hx group. On the day of and on days 1, 2, 3 and 7 after hepatectomy, the liver weight, DNA synthesis rate, biliary lipids excretion rates, and bile acid composition were determined. In the ID-Hx group, the DNA synthesis rate and relative liver weight were significantly higher than those of the OJ-Hx and ED-Hx groups. The excretion rates of biliary lipids were disturbed in the ED-Hx group compared with those in the ID-Hx group and the values in the OJ-Hx group were in-between the ID-Hx and ED-Hx group. The liver regeneration rate was significantly correlated with bile flow and excretion rates of biliary lipids. The maintenance of enterohepatic circulation of biliary lipids before hepatectomy may be important for the liver regeneration.

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“…Internal biliary drainage is superior to external biliary drainage stimulating more liver regeneration demonstrated by an increased rate of hepatic DNA synthesis, liver function, liver weight, bile flow, bile salt and phospholipid secretion in the internally drained group [64][65][66] . External biliary drainage markedly suppresses regenerative capacity [67] , while with internal biliary drainage it is preserved [64] . This suggested that the bile itself contains important factors that are involved in hepatocyte regeneration, and that these factors are irreversibly removed by external drainage with adverse effects on liver regeneration.…”

Section: Biliary Drainagementioning

confidence: 99%

Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications

et al. 2010

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Introduction: The aim of this review is to summarize the available evidence for changes in bile composition following liver surgery and assess their use in predicting post-operative complications. Materials and Methods: A literature search was undertaken for all studies focusing on bile composition, bile volume and analysis. Articles were selected from MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases up to May 2009. Results: Low values of pre-operative bilirubin diglucuronide predict reduced post-operative liver function and the occurrence of jaundice. Low concentrations of hepatocyte growth factor and interleukin-6 in bile following surgery are associated with the subsequent development of liver failure and are probably surrogate markers for situations where the resultant hepatic regeneration is inadequate. Conclusions: Analysis of the composition and quality of bile is probably underused as a tool for the pre-operative screening and early post-operative monitoring of patients at high risk of developing liver failure following major hepatobiliary procedures.

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Decrease in Regeneration Capacity of Rat Liver after External Biliary Drainage

Cited by 33 publications

References 18 publications

An Evaluation of the Influence of Devazepide and CCK-8S on the Intact and Resected Rat Liver

An Evaluation of the Influence of Devazepide and CCK-8S on the Intact and Resected Rat Liver

Differences in Biliary Lipid Excretion after Major Hepatectomy in Obstructive Jaundiced Rats with Preoperative Internal, External, or No Biliary Drainage

Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications

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