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The role of bile salt toxicity in the pathogenesis of bile duct injury after non-heart-beating porcine liver transplantation.
- Source :
-
Transplantation [Transplantation] 2008 Jun 15; Vol. 85 (11), pp. 1625-31. - Publication Year :
- 2008
-
Abstract
- Background: Intrahepatic bile duct strictures are a serious complication after non-heart-beating (NHB) liver transplantation. Bile salt toxicity has been identified as an important factor in the pathogenesis of bile duct injury and cholangiopathies. The role of bile salt toxicity in the development of biliary strictures after NHB liver transplantation is unclear.<br />Methods: In a porcine model of NHB liver transplantation, we studied the effect of different periods of warm ischemia in the donor on bile composition and subsequent bile duct injury after transplantation. After induction of cardiac arrest in the donor, liver procurement was delayed for 0 min (group A), 15 min (group B), or more or equal to 30 min (group C). Livers were subsequently transplanted after 4 hr of cold preservation. In the recipients, bile flow was measured, and bile samples were collected daily to determine the bile salt-to-phospholipid ratio. Severity of bile duct injury was semiquantified by using a histologic grading scale.<br />Results: Posttransplantation survival was directly related to the duration of warm ischemia in the donor. The bile salt-to-phospholipid ratio in bile produced early after transplantation was significantly higher in group C, compared with group A and B. Histopathologic condition showed the highest degree of bile duct injury in group C.<br />Conclusion: Prolonged warm ischemia in NHB donors is associated with the formation of toxic bile after transplantation, with a high biliary bile salt-to-phospholipid ratio. These data suggest that bile salt toxicity contributes to the pathogenesis of bile duct injury after NHB liver transplantation.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B biosynthesis
ATP Binding Cassette Transporter, Subfamily B genetics
ATP Binding Cassette Transporter, Subfamily B, Member 11
ATP-Binding Cassette Transporters biosynthesis
ATP-Binding Cassette Transporters genetics
Animals
Bile Acids and Salts metabolism
Biopsy
Cholestasis, Intrahepatic metabolism
Cholestasis, Intrahepatic mortality
Disease Models, Animal
Female
Gene Expression
Liver Transplantation mortality
Liver Transplantation pathology
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Severity of Illness Index
Survival Rate
Swine
Bile Acids and Salts toxicity
Bile Ducts, Intrahepatic injuries
Cholestasis, Intrahepatic etiology
Liver Transplantation adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 85
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 18551070
- Full Text :
- https://doi.org/10.1097/TP.0b013e318170f5f7