1. An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation
- Author
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Eric Levesque, Mara Disabato, Hassen Hentati, Ismail Ben Mosbah, Daniel Azoulay, Philippe Compagnon, Cyrille Feray, Julien Calderaro, Anne Corlu, José L. Cohen, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioprédic International, Eusapharma (Limonest, France) partly funded the experimental work. Bridge to Life 'Europe' (Ltd, London, United Kingdom) graciously provided the preservation solution for machine perfusion., Jonchère, Laurent, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hépato-biliaire - CHB [Paul Brousse, Paris], Université Paris-Sud - Paris 11 (UP11) - AP-HP Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, Department of Pathology, Centre hospitalier universitaire Henri Mondor, F-94000 Créteil, France, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris 13 - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive Hépato-Billiaire [Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
- Subjects
endoplasmic-reticulum stress ,Time Factors ,medicine.medical_treatment ,Sus scrofa ,030230 surgery ,Liver transplantation ,Potassium Chloride ,0302 clinical medicine ,Liver Function Tests ,Materials Testing ,Mannitol ,sinusoidal endothelial-cells ,cardiac death donors ,Donor pool ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,warm ischemia ,medicine.diagnostic_test ,hope protects ,Graft Survival ,donation ,Pig model ,Equipment Design ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Allografts ,reperfusion injury ,Warm ischemia ,Circulatory death ,3. Good health ,Perfusion ,Liver ,Cardiology ,Female ,030211 gastroenterology & hepatology ,medicine.medical_specialty ,criteria donor livers ,preservation ,Organ Preservation Solutions ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,medicine ,Animals ,Hepatectomy ,Tissue Survival ,Transplantation ,Machine perfusion ,medicine.disease ,static cold-storage ,Heart Arrest ,Liver Transplantation ,Surgery ,Disease Models, Animal ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Glucose ,Energy Metabolism ,Liver function tests ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Reperfusion injury ,Biomarkers ,Procaine - Abstract
International audience; BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. RESULTS: All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. CONCLUSIONS: This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.
- Published
- 2017
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