Observations and findings during the development of a subnormothermic/normothermic long‐term ex vivo liver perfusion machine

Schüler, Martin; Becker, Dustin; Mueller, Matteo; Borrego, Lucía Bautista; Mancina, Leandro; Huwyler, Florian; Binz, Jonas; Hagedorn, Catherine; Schär, Beatrice; Gygax, Erich; Weisskopf, Miriam; Silva, Richard Xavier Sousa Da; Crisóstomo, João Miguel Antunes; Dutkowski, Philipp; Rohr, Philipp Rudolf von; Clavien, Pierre‐Alain; Tibbitt, Mark W.; Eshmuminov, Dilmurodjon; Hefti, Max

doi:10.1111/aor.14403

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…This might be due to the mechanical damage to red blood cells caused by the long-term peristaltic pump perfusion, leading to hemolysis. 34 Subsequently, a large number of erythrocytic ions and enzymes, such as potassium ions and LDH were released, leading to the continuous increase in the measured values of these 3 substances, 35 and their values did not decrease until the perfusate was changed. This might cause significant changes in the osmotic pressure of perfusate, resulting in tissue edema and weight gain.…”

Section: Discussionmentioning

confidence: 99%

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

Yang

Zhang

Song

et al. 2024

Chinese Journal of Traumatology

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Section: Discussionmentioning

confidence: 99%

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

Yang

Zhang

Song

et al. 2024

Chinese Journal of Traumatology

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“…Erythrocyte damage and haemolysis are common sequelae of extracorporeal perfusion platforms, resulting in RBC depletion and therewith free haemoglobin accumulation (18). Whereas the liver can convert free haemoglobin into bilirubin and excrete it into bile during multi-day perfusion (11,19), free haemoglobin will accumulate during kidney perfusion. This poses a serious problem given that the kidney is extremely susceptible to supraphysiological levels of cell free haemoglobin, with acute kidney injury (AKI) as a common consequence (20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Advancing multi-day ex vivo kidney perfusion using spatially resolved metabolomics

Haan

Witjas

Graaf

et al. 2023

Preprint

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The ability to preserve metabolically active kidneys ex vivo for multiple days may permit reconditioning, repair and regeneration of deceased donor kidneys. However, the kidneys high metabolic demand limits its functional preservation. Current approaches focus on normothermic machine perfusion (NMP) at 37C or hypothermic machine perfusion (HMP) at 4-8C. At normothermia, kidneys are metabolically active but ex vivo preservation is limited to hours. During hypothermia kidneys can be preserved up to 24 hours but are metabolically inactive and suffer cold-induced injury. Therefore, we revisited sub normothermic perfusion (at 25C) as an alternative approach to preserve human kidneys in a metabolically active state for extended periods of time. In a custom-made platform that includes a cell-free perfusate enriched with TCA cycle fuels, urine recirculation, and continuous hemofiltration we perfused discarded human kidneys up to 8 days. Using spatially resolved single cell resolution isotope tracing we demonstrate active metabolism in all the different renal cell types over this period. However, beyond 4 days cell composition of nephron segments assessed with spatial lipidomics changed substantially and injury markers such as NGAL and LDH increased in the perfusate. Up to 4 days, perfused human discarded donor kidneys maintained metabolic fluxes, functional parameters and allow for reperfusion using a porcine auto transplantation model. These data underpin that extended multi-day metabolic preservation of human kidneys is achievable using a sub normothermic perfusion platform.

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“…In addition to the varying cutoff values, controversy exists on whether lactate clearance is an accurate marker of graft viability. The Zurich group showed lactate clearance up to 24 h of NMP in four explant cirrhotic livers, questioning the predictive value of lactate clearance in early assessment[37…”

mentioning

confidence: 99%

Viability assessment of the liver during ex-situ machine perfusion prior to transplantation

Groen,

van Leeuwen,

de Jonge

et al. 2024

Current Opinion in Organ Transplantation

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Purpose of review In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function. Recent findings Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy. Summary Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.

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Observations and findings during the development of a subnormothermic/normothermic long‐term ex vivo liver perfusion machine

Cited by 5 publications

References 54 publications

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

Advancing multi-day ex vivo kidney perfusion using spatially resolved metabolomics

Viability assessment of the liver during ex-situ machine perfusion prior to transplantation

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