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21 October 2016 : Original article  

Neither Isolated Hepatic Arterial Clamping nor Hepatic Arterial Ligation Induce Ischemic Type Biliary Lesions in Rats

Ulrich KepplerBCDEF, Mohammed R. MoussavianAF, Pascal JeanmonodF, Moritz J. StrowitzkiCDF, Mathias WagnerD, Claudia ScheuerCD, Michael D. MengerADE, Maximilian von HeesenACDE

DOI: 10.12659/AOT.898001

Ann Transplant 2016; 21:649-659

Abstract

BACKGROUND: Ischemic type biliary lesions (ITBL) is a troublesome complication after liver transplantation. Little is known about its pathogenesis and there is particularly little data about morphological alterations. Prolonged warm and cold ischemia time and reduced hepatic arterial perfusion are risk factors leading to ITBL. There are only a few animal models described in literature. Therefore, we examined the effects of 3 h of hepatic artery ischemia-reperfusion (3 h I/R) and hepatic arterial ligation (HAL), both combined with ligation of the peribiliary plexus (PBP).

MATERIAL AND METHODS: 3 h I/R was performed by clamping the hepatic artery with microvascular clamps for 3 h. HAL was performed by ligation of the hepatic artery. Both procedures were combined with stenting of the common bile duct with double ligation of the PBP. A sham group without clamping served as control. Serum activities of aspartate transaminase (AST) and alanine transaminase (ALT), direct and total bilirubin (DB/TB), and lactate dehydrogenase (LDH) were measured. Bile flow was analyzed and histological examinations of leukocyte infiltration (CAE), cell proliferation (PCNA), apoptotic cells (HE), and bile ducts morphology (CK7) were performed. Western blots of the vascular endothelial growth factor (VEGF) and caspase 3 were made to investigate vascular growth expression and apoptotic cell death.

RESULTS: 3 h I/R and HAL were associated with a significant hepatocellular injury and inflammation, shown through increased AST and ALT, leukocyte infiltration, and apoptotic cell death. An increase of bile ducts and a reduction of arteries/bile duct ratio after 30 days was observed in the 3 h I/R group and HAL, but no ITBL-typical bile duct necrosis, intrahepatic strictures, or dilatations of bile ducts occurred.

CONCLUSIONS: Morphological alterations in a rat animal model of 3 h I/R and HAL could be demonstrated. However, a model of intrahepatic biliary lesions could not be established through hepatic arterial ligation or through 3-h hepatic arterial ischemia and reperfusion.

Keywords: Cholestasis, Hepatic Artery, Liver Transplantation, Models, Animal, Reperfusion Injury

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358