An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation

Philippe Compagnon (1, 2) , Eric Levesque (2, 1) , Hassen Hentati (2, 1) , Mara Disabato (2) , Julien Calderaro (2) , Cyrille Feray (2) , Anne Corlu (3) , José Laurent Cohen (1) , Ismail Ben Mosbah (4, 1) , Daniel Azoulay (2)

1 IMRB - Institut Mondor de Recherche Biomédicale
2 Hôpital Henri Mondor
3 NuMeCan - Nutrition, Métabolismes et Cancer
4 Bioprédic International

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.

Keywords: endoplasmic-reticulum stress; sinusoidal endothelial-cells; criteria donor livers; cardiac death donors; static cold-storage; reperfusion injury; hope protects; warm ischemia; preservation

Keywords: donation

Domains: Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Food and Nutrition; Life Sciences [q-bio]; Human health and pathology; Endocrinology and metabolism

Philippe Compagnon, Eric Levesque, Hassen Hentati, Mara Disabato, Julien Calderaro, et al.. An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation. Transplantation, 2017, 101 (7), pp.e205-e213. ⟨10.1097/TP.0000000000001764⟩. ⟨hal-01560561⟩