Warm vs. cold perfusion techniques to rescue rodent liver grafts.

Abstract

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.

• Authors: Andrea Schlegel, Philipp Kron, Rolf Graf, Philipp Dutkowski, Pierre-Alain Clavien
• Journal: Journal of hepatology (J Hepatol) Vol. 61 Issue 6 Pg. 1267-75 (Dec 2014) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25086285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Topics

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