Evidence map›Paper›PMID 32979838›Full record

ArticleEBioMedicine2020

Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation.

Andrea Schlegel, Xavier Muller, Matteo Mueller, Anna Stepanova, Philipp Kron, Olivier de Rougemont, Paolo Muiesan, Pierre-Alain Clavien, Alexander Galkin, David Meierhofer and 1 more

Abstract read
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  19. Small animalWorld journal of gastroenterology · 2026
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55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Andrea SchlegelDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland; Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, UK.
Xavier MullerDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland.
Matteo MuellerDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland.
Anna StepanovaColumbia University, Department of Pediatrics, 650 W 168th St, New York, NY 10032, U.S.A.
Philipp KronDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland.
Olivier de RougemontDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland.
Paolo MuiesanLiver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, UK.
Pierre-Alain ClavienDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland.
Alexander GalkinColumbia University, Department of Pediatrics, 650 W 168th St, New York, NY 10032, U.S.A.
David MeierhoferMax Planck Institute for Molecular Genetics, Mass Spectrometry Facility, Berlin, Germany.
Philipp DutkowskiDepartment of Surgery and Transplantation, University Hospital Zurich, Switzerland. Electronic address: philipp.dutkowski@usz.ch.

Funding

The Role of FMN Loss by Mitochondrial Complex I in Neonatal Hypoxic-Ischemic Brain InjuryR01NS112381 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GALKIN, ALEXANDER · 2020 to 2024
$2.1M
NINDS NIH HHS R01 NS112381
6 · The paper itself

Abstract

backgroundMitochondrial succinate accumulation has been suggested as key event for ischemia reperfusion injury in mice. No specific data are however available on behavior of liver mitochondria during ex situ machine perfusion in clinical transplant models.

methodsWe investigated mitochondrial metabolism of isolated perfused rat livers before transplantation. Livers were exposed to warm and cold ischemia to simulate donation after circulatory death (DCD) and organ transport. Subsequently, livers were perfused with oxygenated Belzer-MPS for 1h, at hypothermic or normothermic conditions. Various experiments were performed with supplemented succinate and/or mitochondrial inhibitors. The perfusate, liver tissues, and isolated mitochondria were analyzed by mass-spectroscopy and fluorimetry. Additionally, rat DCD livers were transplanted after 1h hypothermic or normothermic oxygenated perfusion. In parallel, perfusate samples were analysed during HOPE-treatment of human DCD livers before transplantation.

findingsSuccinate exposure during rat liver perfusion triggered a dose-dependent release of mitochondrial Flavin-Mononucleotide (FMN) and NADH in perfusates under normothermic conditions. In contrast, perfusate FMN was 3-8 fold lower under hypothermic conditions, suggesting less mitochondrial injury during cold re-oxygenation compared to normothermic conditions. HOPE-treatment induced a mitochondrial reprogramming with uploading of the nucleotide pool and effective succinate metabolism. This resulted in a clear superiority after liver transplantation compared to normothermic perfusion. Finally, the degree of mitochondrial injury during HOPE of human DCD livers, quantified by perfusate FMN and NADH, was predictive for liver function.

interpretationMitochondrial injury determines outcome of transplanted rodent and human livers. Hypothermic oxygenated perfusion improves mitochondrial function, and allows viability assessment of liver grafts before implantation.

fundingdetailed information can be found in Acknowledgments.

Indexed as

Hypothermia, InducedLiver TransplantationPerfusionTransplantation ConditioningAnimalsBiomarkersCellular ReprogrammingElectron Transport Chain Complex ProteinsEnergy MetabolismHumansLiverLiver Function TestsMitochondriaModels, AnimalNADNADPBiomarkersElectron Transport Chain Complex ProteinsNADNADPOxygenComplex IFMNHypothermic oxygenated perfusionLiver transplantationNormothermic oxygenated perfusion

Identifiers

PMID32979838
PMCPMC7519249

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.