Hypothermic Oxygenated Perfusion in Transplantation
Although hypothermic oxygenated liver perfusion (HOPE) was known to increase the cellular energy content for many years, a broader understanding of the underlying protective mechanism was only discovered recently. During cold tissue oxygenation, mitochondria can recover from previous ischemic injury, metabolise accumulated succinate and reprogram their complex proteins for a more coordinated electron flow and slow succinate metabolism at normothermic reperfusion. Further protection from the well-known inflammatory response, occurring when mammalian tissues undergo immediate reperfusion after static cold storage, is another positive effect. The excellent results from recent clinical studies appear well-understood in context of this protective mechanism.
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Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed.
The field of liver transplantation has recently seen a boost in the development of machine perfusion technology with the first randomized controlled trials published and the availability of several devices on the market. To further drive this technology successfully into routine clinical practice, the community needs to first understand underlying mechanisms of protection by different perfusion approaches. Secondly, transparent reports of study results and the identification of gaps in the literature are needed. With this review article we summarize the clinical studies on hypothermic machine perfusion (HMP) in liver transplantation. Next, the protective mechanism of this cold oxygenation is described. Third, a few methodological differences of HMP performed by different groups are identified and discussed followed by the impact of HMP on organ selection through viability assessment. Finally, this review will project future trials needed to answer the here described ambiguities.
3.What Is the Real HOPE-Effect in Solid Organ Transplantation?
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