Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

Schlegel, Andrea; Kron, Philipp; Dutkowski, Philipp

doi:10.1007/s40472-014-0046-1

Cited by 68 publications

(70 citation statements)

References 86 publications

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“…10 Our study demonstrates that HOPE prevents oxidative stress or DAMPs release during perfusion. 8,10,24 In addition, HOPE treatment prevents mitochondrial ROS production and downstream macrophage and endothelial activation during reperfusion, 8,29 potentially by a reversible downregulation of mitochondrial electron transfer. 8 Accordingly, kidney grafts treated by HOPE showed significant less TLR-4-positive cells, less TNF-a release, less endothelial cell activation after implantation, and were rescued from lethal injury, in contrast to normothermic perfusion or cold storage alone.…”

Section: Discussionmentioning

confidence: 99%

Short, Cool, and Well Oxygenated – HOPE for Kidney Transplantation in a Rodent Model

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Short, Cool, and Well Oxygenated – HOPE for Kidney Transplantation in a Rodent Model

et al. 2016

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“…Previous work, however, confirmed that hypothermic liver perfusion with completely deoxygenated perfusate failed to protect from reperfusion injury [22,29 & ]. Of note, the rate of oxygen consumption during HOPE is not stable but decreases rapidly during the first hour, and ceases after 90 min at a low baseline level [13,22,34]. This effect relates to a decrease of electron-rich substrates during hypothermic oxygenation [22].…”

Section: Oxygenmentioning

confidence: 97%

“…Therefore, the concept of machine perfusion instead of conventional static cold storage has been nowadays revisited to improve graft viability [12]. The concurring machine perfusion strategies for livers differ in perfusate conditions, including particularly temperature and timing of perfusion [13,14]. In this review, we summarize recent developments in the field of hypothermic machine liver perfusion, and focus on clinical application in humans.…”

Section: Introductionmentioning

confidence: 99%

Hypothermic machine perfusion in liver transplantation

Schlegel

Kron

Dutkowski

2016

Current Opinion in Organ Transplantation

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Purpose of the reviewThe purpose of the review is to report recent human application of hypothermic machine liver perfusion, and to discuss potential protective mechanisms. Recent findingsHuman application of hypothermic machine liver perfusion is still very limited. Currently, three transplant centers apply this novel treatment in donation after cardiac death (DCD) or donation after brain death (DBD) liver grafts. In all cases, endischemic perfusion was performed after initial cold storage for organ transport. Perfusion conditions differ slightly in terms of oxygenation (pO 2 15-60 kPa), perfusion route (dual vs. portal), perfusion time (2-4 h), and perfusate. SummaryThe current data support the hypothesis that applying endischemic hypothermic machine liver perfusion protects extended criteria DBD and DCD livers from initial reperfusion injury, with better graft function and less biliary complications. Hypothermic machine perfusion may therefore offer revitalization of liver grafts before implantation by a simple and practical perfusion technique with a high impact on enlarging the donor pool. Multicentric phase III randomized control trials in DBD and DCD liver transplantation have been initiated to further test this strategy, which may establish machine liver perfusion in the clinical setting.

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“…Oxygenated machine perfusion has many advantages over hypothermic machine perfusion. It can protect liver grafts exposed to warm and cold ischemia [44] and can efficiently deliver nutrients and oxygen into the core of the organ under appropriate conditions. The extracorporeal membrane oxygenation technology has been used sporadically in controlled DCD donors under normothermic [45,46] and subnormothermic [47] conditions.…”

Section: Discussionmentioning

confidence: 99%

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

Murakami²,

Aoki³

et al. 2015

Eur Surg Res

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Background: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. Materials and Methods: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. Results: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. Conclusion: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

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Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

Cited by 68 publications

References 86 publications

Short, Cool, and Well Oxygenated – HOPE for Kidney Transplantation in a Rodent Model

Short, Cool, and Well Oxygenated – HOPE for Kidney Transplantation in a Rodent Model

Hypothermic machine perfusion in liver transplantation

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

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