title: Addition of carvedilol to University Wisconsin solution improves rat steatotic and nonsteatotic liver preservation.
abstract: Here we examine the effect of adding carvedilol (CVD) to University of Wisconsin (UW) solution on the preservation of steatotic and nonsteatotic livers during cold ischemia and after normothermic reperfusion. We used an isolated perfused rat liver model. The following protocols were evaluated. Protocol 1 concerned the effect of CVD after cold ischemia. Steatotic and nonsteatotic livers were preserved for 24 hours in UW solution alone or with CVD. Livers without cold ischemia were used as controls. Transaminases were evaluated in the flushing effluent. Protocol 2 involved the effect of CVD after reperfusion. Both liver types were preserved for 24 hours in UW solution alone or with CVD and then perfused ex vivo for 2 hours at 37 degrees C. Livers flushed and perfused without ischemia were used as controls. Hepatic injury and functionality [transaminases, bile production, and hepatic clearance of sulfobromophthalein (BSP)] were evaluated after reperfusion. In addition, factors potentially involved in hepatic ischemia-reperfusion injury, including oxidative stress (malondialdehyde and superoxide anion levels), mitochondrial damage (glutamate dehydrogenase activity), microcirculatory disorders (flow rate and vascular resistance), and adenosine triphosphate (ATP) depletion, were evaluated after reperfusion. After cold ischemia, steatotic livers preserved in UW solution showed higher transaminase levels than nonsteatotic livers. After reperfusion, steatotic livers preserved in UW solution showed higher transaminase levels and lower bile production and BSP clearance than nonsteatotic livers. Alterations in the perfusion flow rate and vascular resistance, mitochondrial damage, and reduced ATP content were more evident in steatotic livers preserved in UW solution. The addition of CVD to UW solution reduced hepatic injury, obstructed its mechanisms, and improved hepatic functionality in both liver types. We conclude that CVD is a useful additive for UW solution that improves the preservation of steatotic and nonsteatotic livers subjected to prolonged cold ischemia.
authors.affiliation: Department of Experimental Pathology Department, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, 08036 Barcelona, Spain.
authors.forename: Ismail
authors.initials: I
authors.lastname: Ben Mosbah
authors.forename: Joan
authors.initials: J
authors.lastname: Roselló-Catafau
authors.forename: Izabel
authors.initials: I
authors.lastname: Alfany-Fernandez
authors.forename: Antoni
authors.initials: A
authors.lastname: Rimola
authors.forename: Pera Puig
authors.initials: PP
authors.lastname: Parellada
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mitjavila
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
authors.forename: Hassen
authors.initials: H
authors.lastname: Ben Abdennebi
authors.forename: Olivier
authors.initials: O
authors.lastname: Boillot
authors.forename: Juan
authors.initials: J
authors.lastname: Rodés
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003080:Cold Temperature; D005234:Fatty Liver / Q000517:prevention & control*; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008111:Liver Function Tests; D016031:Liver Transplantation; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control; D011412:Propanolamines / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000517:prevention & control; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D007328:Insulin; D019188:Organ Preservation Solutions; D011412:Propanolamines; C055206:University of Wisconsin-lactobionate solution; D000077261:Carvedilol; D000493:Allopurinol; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose