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 Jul;101(7):e205-e213. doi: 10.1097/TP.0000000000001764.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Energy Metabolism
  • Equipment Design
  • Female
  • Glucose / pharmacology
  • Graft Survival
  • Heart Arrest / chemically induced
  • Hepatectomy* / adverse effects
  • Liver / metabolism
  • Liver / pathology
  • Liver / surgery*
  • Liver Function Tests
  • Liver Transplantation / adverse effects
  • Liver Transplantation / instrumentation*
  • Liver Transplantation / methods
  • Mannitol / pharmacology
  • Materials Testing
  • Organ Preservation Solutions / pharmacology
  • Perfusion / adverse effects
  • Perfusion / instrumentation*
  • Perfusion / methods
  • Potassium Chloride / pharmacology
  • Procaine / pharmacology
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Sus scrofa
  • Time Factors
  • Tissue Survival
  • Warm Ischemia / adverse effects
  • Warm Ischemia / instrumentation*
  • Warm Ischemia / methods

Substances

  • Biomarkers
  • Bretschneider cardioplegic solution
  • Organ Preservation Solutions
  • Mannitol
  • Procaine
  • Potassium Chloride
  • Glucose