Metformin Preconditioning Improves Hepatobiliary Function and Reduces Injury in a Rat Model of Normothermic Machine Perfusion and Orthotopic Transplantation

Autor: Robert J. Porte, Ton Lisman, Masato Fujiyoshi, Andrie C. Westerkamp, Henri G. D. Leuvenink, Han Moshage, Petra J. Ottens, Tim A Berendsen, Vincent E de Meijer, Maarten W. N. Nijsten, Daan J Touw
Přispěvatelé: Microbes in Health and Disease (MHD), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Pharmaceutical Analysis, Groningen Research Institute for Asthma and COPD (GRIAC), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Nanomedicine & Drug Targeting, Groningen Institute for Organ Transplantation (GIOT), Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Medicinal Chemistry and Bioanalysis (MCB)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
medicine.medical_specialty
Transplantation Conditioning
Bilirubin
medicine.medical_treatment
Urology
Cold storage
030230 surgery
Liver transplantation
BILE-DUCT INJURY
MECHANISMS
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
LEFT-VENTRICULAR FUNCTION
medicine
Animals
Lactic Acid
Original Basic Science—Liver
Biliary Tract
Cholesterol 7-alpha-Hydroxylase
ATP Binding Cassette Transporter
Subfamily B
Member 11
Transplantation
Machine perfusion
business.industry
ACTIVATED PROTEIN-KINASE
Organ Preservation
LIVER-TRANSPLANTATION
Metformin
APOPTOSIS
Liver Transplantation
Rats
Perfusion
Bicarbonates
chemistry
MYOCARDIAL-INFARCTION
Rats
Inbred Lew
Models
Animal
HEART
030211 gastroenterology & hepatology
GRAFTS
Liver function
business
FARNESOID-X-RECEPTOR
medicine.drug
Zdroj: Transplantation
Transplantation, 104(9), E271-E280. LIPPINCOTT WILLIAMS & WILKINS
ISSN: 1534-6080
0041-1337
Popis: Background. Preconditioning of donor livers before organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation. Methods. Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours. Graft assessment was performed using NMP via double perfusion of the hepatic artery and portal vein. In an additional experiment, rat donor livers preconditioned with metformin were stored on ice for 4 hours and transplanted to confirm postoperative liver function and survival. Data were analyzed and compared with sham-fed controls. Results. Graft assessment using NMP confirmed that preconditioning significantly improved ATP production, markers for hepatobiliary function (total bile production, biliary bilirubin, and bicarbonate), and significantly lowered levels of lactate, glucose, and apoptosis. After orthotopic liver transplantation, metformin preconditioning significantly reduced transaminase levels. Conclusions. Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation.
Databáze: OpenAIRE
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