Warm vs. cold perfusion techniques to rescue rodent liver grafts

J Hepatol. 2014 Dec;61(6):1267-75. doi: 10.1016/j.jhep.2014.07.023. Epub 2014 Jul 31.


Background & aims: A variety of liver perfusion techniques have been proposed to protect liver grafts prior to implantation. We compared hypothermic and normothermic oxygenated perfusion techniques in a rat liver transplant model, using higher risk grafts obtained after cardiac arrest (DCD).

Methods: Rat livers were subjected to 30 or 60 min in situ warm ischemia, without application of heparin. Livers were excised and stored for 4 h at 4°C, mimicking DCD organ procurement, followed by conventional organ transport. In experimental groups, DCD liver grafts received a 4 h normothermic oxygenated perfusion through the portal vein and the hepatic artery instead of cold storage. The perfusate consisted of either full blood or leukocyte-depleted blood (normothermic groups). Other livers underwent hypothermic oxygenated perfusion (HOPE) for 1 h after warm ischemia and 4 h cold storage (HOPE group). Liver injury was assessed during machine perfusion and after isolated liver reperfusion, and by orthotopic liver transplantation (OLT).

Results: DCD livers, subjected to normothermic perfusion, disclosed reduced injury and improved survival compared to cold storage after limited warm ischemia of 30 min (70%; 7/10), but failed to protect from lethal injury in grafts exposed to 60 min warm ischemia (0%; 0/10). This finding was consistent with Kupffer and endothelial cell activation in cold stored and normothermic perfused livers. In contrast, HOPE protected from hepatocyte and non-parenchymal cell injury and led to 90% (9/10) and 63% (5/8) animal survival after 30 and 60 min of donor warm ischemia, respectively.

Conclusions: This is the first evidence that HOPE is superior to normothermic oxygenated perfusion in a clinically relevant model through modulation of the innate immunity and endothelial cell activation.

Keywords: DCD liver; Hypothermic oxygenated perfusion; Liver transplantation; Normothermic oxygenated liver perfusion; Survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cold Ischemia*
  • Endothelial Cells / physiology
  • Immunity, Innate / physiology
  • Liver / blood supply
  • Liver / pathology
  • Liver / physiology
  • Liver Transplantation / methods*
  • Male
  • Models, Animal
  • Perfusion / methods*
  • Rats, Inbred BN
  • Survival Rate
  • Temperature*
  • Time Factors
  • Warm Ischemia*