title: An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 2 Institut Mondor Recherche Biomédicale (IMRB), Université Paris-Est, Créteil, France. 3 Service de Réanimation Digestive, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 4 Service d'Anatomopathologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 5 Service d'Hépatologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 6 INSERM, Univ Rennes, INRA, Nutrition Metabolisms and Cancer (NuMeCan), Rennes, France. 7 Biopredic International, Rennes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Compagnon
authors.forename: Eric
authors.initials: E
authors.lastname: Levesque
authors.forename: Hassen
authors.initials: H
authors.lastname: Hentati
authors.forename: Mara
authors.initials: M
authors.lastname: Disabato
authors.forename: Julien
authors.initials: J
authors.lastname: Calderaro
authors.forename: Cyrille
authors.initials: C
authors.lastname: Feray
authors.forename: Anne
authors.initials: A
authors.lastname: Corlu
authors.forename: José Laurent
authors.initials: JL
authors.lastname: Cohen
authors.forename: Ismail
authors.initials: I
authors.lastname: Ben Mosbah
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
mesh_terms: D064591:Allografts; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism; D004867:Equipment Design; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival; D006323:Heart Arrest / Q000139:chemically induced; D006498:Hepatectomy / Q000009:adverse effects; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D008353:Mannitol / Q000494:pharmacology; D008422:Materials Testing; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010477:Perfusion / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D034421:Sus scrofa; D013997:Time Factors; D014022:Tissue Survival; D052096:Warm Ischemia / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods
chemical_list: D015415:Biomarkers; C039984:Bretschneider cardioplegic solution; D019188:Organ Preservation Solutions; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose