HYPOTHERMIC MACHINE PERFUSION OF THE LIVER. THE REASONS FOR SUCCESS

Abstract

Machine perfusion is an attractive preservation technique to improve outcomes after transplantation. Based on underlying protective mechanisms two main concepts are described today, both with the same goal to provide oxygen to ischemic tissue. While normothermic machine perfusion (NMP) is rather labor intense and conveys its highest effect when performed instead of cold storage, the concept of hypothermic machine perfusion (HMP) is simpler and used after cold storage in the recipient centre. During re-oxygenation mitochondria immediately initiate the inflammatory cascade of ischemia-reperfusion-injury (IRI), although those features appear significantly less pronounced under cold conditions. In contrast to a normothermic perfusion, hypothermic techniques lead to a functional recovery of the respiratory chain and the Krebs cycle, thereby reloading cellular energy and metabolizing toxic metabolites, including Succinate. Although the preconditioning of mitochondria with cold oxygenation prior to transplantation is repeatedly described since the early days of organ transplantation, an increasing body of supportive literature is seen only recently. Newly published randomized controlled trials confirm this protection and demonstrate less organ injury, less complications including non-anastomotic biliary strictures, lower acute rejection rates and better graft survivals with the use of hypothermic oxygenated perfusion (HOPE). Of great interest is also the simplicity of HOPE, particularly when applied through the portal vein only, enabling the performance of a liver split during perfusion without the risk of arterial injury. In addition, there is increasing evidence how to assess liver viability during HMP through real-time spectroscopy of mitochondrial metabolism. Perfusate levels of Flavin mononucleotide (FMN), released from complex-I during reperfusion correlate with posttransplant complications and graft survival. This review article describes all features of HMP and addresses remaining challenges of this beneficial preservation technique.