Extended hypothermic oxygenated machine perfusion enables ex situ preservation of porcine livers for up to 24 hours

Abstract

Static cold storage Extended hypotermic oxygenated machine perfusion enables ex situ preservation of porcine livers for up to 24 h Dynamic preservation with DHOPE Reperfusion and viability assessment 2 h SCS 2 h DHOPE 4 h reperfusion 2 h SCS 6 h DHOPE 4 h reperfusion 2 h SCS 24 h DHOPE 4 h reperfusion 8-11 h SCS 20 h DHOPE 3 h reperfusion 24 h SCS 4 h reperfusion Decreasing venous and arterial flows, no bile production, injured appearence Non-viable livers • Lactate clearance, blood pH, glucose, ALT • Biliary pH, bicarbonate, LDH • HMGB-1, IL-6, TNFα, cfDNA • Bile duct and liver parenchyma histology Viable livers, all with similar: Lactate <1.7 mmol/L, perfusate pH7.35-7.45, bile production >10 ml, biliary pH >7.45 Livers meet viability criteria during 2.5 h Highlights DHOPE can be extended for up to 24 h to prolong donor liver preservation time. Hepatocellular and biliary function is maintained after ex situ preservation by 24 h DHOPE. Extension of DHOPE for up to 24 h does not induce more injury compared to shorter preservation times. The initial results of extended preservation by DHOPE for discarded human livers are promising. Lay summary It has been suggested that preserving liver grafts with a technique called (dual) hypothermic oxygenated machine perfusion ([D]HOPE) leads to better outcomes after transplantation than if livers are stored on ice, especially if an organ is of lesser quality. In this study, we showed that DHOPE could be used to preserve liver grafts for up to 24 h. This extended procedure could be used globally to facilitate transplantation and expand the donor pool.

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

“…As a consequence, in the last decade, the hypothermic oxygenated perfusion (HOPE) has been implemented as a complementary tool to improve graft preservation [36][37][38][39]. This strategy combines the benefits of cold preservation conditions with the presence of a transient oxygen supply to the organ in a perfusion system, with the purpose to help the mitochondrial system to sustain a basic level of oxidative phosphorylation, which in turn will provide the organ with better conditions to face the unavoidable reperfusion [36][37][38][39]. In contrast to static preservation, the fluid dynamics that intrinsically occurs in any fluid-applying forces in a vascular section, as it happens in HOPE (or any kind of reperfusion), is responsible for generating the phenomenon known as shear stress [40].…”

“…As the same formulation is used throughout this article, we refer to them generically as Belzer MPS. This solution was designed for kidney MP and then extended to liver HOPE strategies [36][37][38][39]. However, the use of Belzer MPS-like solutions in liver MP has some limitations.…”

Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

“…It would be of interest to further investigate the boundaries of extended cold MP. 32 Several studies have been undertaken to elucidate the beneficial effects of oxygenated versus nonoxygenated HMP. In 2005, the first study describing HMP in discarded human livers was published by Guarrera et al, which showed safe preservation of livers without active oxygenation of the MP solution.…”

“…However, several studies demonstrate only minimal oxidative stress during HOPE, even when high oxygen concentrations are used, or when HOPE is extended for longer hours. 19,32,37 Caution should be given to the perfusion devices' pressure settings during HMP, as higher vascular resistances in the cold pose a risk of undesired endothelial shear stress to the liver sinusoids. 38 Some of the currently used perfusion devices are flow-controlled, such as the Medtronic PBS used by Guarrera et al, whereas others are pressure-controlled, like the Liver Assist from Organ Assist used by Porte et al 23,25,28 Based on recent studies, adjusting MP settings to portal pressures of 3 mm Hg and arterial pressures of 25 mm Hg can avoid shear stress.…”

The second volume

“…3 The transplant team in Groningen now document the successful studies of hypothermic oxygenated ex situ perfusion in pig livers over 24 hours with continued viability. 4 The authors postulate that hypothermic oxygenated perfusion might enable prolonged preservation times, thus allowing for better scheduling of the surgery (during the day rather than at ungodly hours of the night) and potentially less expensive transport by commercial airlines rather than chartered jet. The hypothermic perfusion also requires less minute by minute attention.…”