title: Neither Isolated Hepatic Arterial Clamping nor Hepatic Arterial Ligation Induce Ischemic Type Biliary Lesions in Rats.
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.
authors.affiliation: Department of Anaesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keppler
authors.affiliation: Department of General, Vascular and Pediatric Surgery, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Moussavian
authors.affiliation: Department of General, Vascular and Pediatric Surgery, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Jeanmonod
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Moritz J
authors.initials: MJ
authors.lastname: Strowitzki
authors.affiliation: Institute of Pathology, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Intitute for Clinical and Experimental Surgery, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Scheuer
authors.affiliation: Intitute for Clinical and Experimental Surgery, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Department of General, Vascular and Pediatric Surgery, University of Saarland, Homburg/ Saar, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Heesen
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D001659:Biliary Tract / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D003250:Constriction; D004195:Disease Models, Animal; D005260:Female; D006499:Hepatic Artery / Q000473:pathology / Q000601:surgery*; D007511:Ischemia / Q000209:etiology*; D007962:Leukocytes / Q000473:pathology; D008026:Ligation; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods*; D008953:Models, Anatomic; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat