English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation

Schlegel, A., Muller, X., Mueller, M., Stepanova, A., Kron, P., de Rougemont, O., et al. (2020). Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation. EBioMedicine, 60: 103014. doi:10.1016/j.ebiom.2020.103014.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0007-2479-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-247A-8
Genre: Journal Article

Files

show Files
hide Files
:
Schlegel_2020.pdf (Publisher version), 5MB
Name:
Schlegel_2020.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2020 The Author(s)

Locators

show

Creators

show
hide
 Creators:
Schlegel, Andrea, Author
Muller, Xavier , Author
Mueller, Matteo , Author
Stepanova, Anna, Author
Kron, Philipp , Author
de Rougemont, Olivier, Author
Muiesan, Paolo , Author
Clavien, Pierre-Alain , Author
Galkin, Alexander , Author
Meierhofer, David1, Author              
Dutkowski, Philipp , Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

Content

show
hide
Free keywords: FMN Complex I Hypothermic oxygenated perfusion Normothermic oxygenated perfusion Liver transplantation
 Abstract: Background: Mitochondrial succinate accumulation has been suggested as key event for ischemia reperfusioninjury in mice. No specific data are however available on behavior of liver mitochondria duringex situmachine perfusion in clinical transplant models. Methods: We 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 organtransport. Subsequently, livers were perfused with oxygenated Belzer-MPS for 1h, at hypothermic or normo-thermic conditions. Various experiments were performed with supplemented succinate and/or mitochon-drial inhibitors. The perfusate, liver tissues, and isolated mitochondria were analyzed by mass-spectroscopyandfluorimetry. Additionally, rat DCD livers were transplanted after 1h hypothermic or normothermic oxy-genated perfusion. In parallel, perfusate samples were analysed during HOPE-treatment of human DCD liversbefore transplantation. Findings: Succinate exposure during rat liver perfusion triggered a dose-dependent release of mitochondrialFlavin-Mononucleotide (FMN) and NADH in perfusates under normothermic conditions. In contrast, perfus-ate FMN was 3-8 fold lower under hypothermic conditions, suggesting less mitochondrial injury during coldre-oxygenation compared to normothermic conditions. HOPE-treatment induced a mitochondrial reprog-ramming with uploading of the nucleotide pool and effective succinate metabolism. This resulted in a clearsuperiority after liver transplantation compared to normothermic perfusion. Finally, the degree of mitochon-drial injury during HOPE of human DCD livers, quantified by perfusate FMN and NADH, was predictive forliver function. Interpretation: Mitochondrial injury determines outcome of transplanted rodent and human livers. Hypothermicoxygenated perfusion improves mitochondrial function, and allows viability assessment of liver grafts beforeimplantation. Funding: detailed information can be found in Acknowledgments.

Details

show
hide
Language(s): eng - English
 Dates: 2020-09-072020-09-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.ebiom.2020.103014
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: EBioMedicine
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 60 Sequence Number: 103014 Start / End Page: - Identifier: ISSN: 2352-3964
CoNE: https://pure.mpg.de/cone/journals/resource/2352-3964