Meszaros 2022 EBioMedicine
|Meszaros AT, Hofmann J, Buch ML , Cardini B, Dunzendorfer-Matt T, Nardin F, Blumer MJ, Fodor M, Hermann M, Zelger B, Otarashvili G, Schartner M, Weissenbacher A, Oberhuber R, Resch T, Troppmair J, Öfner D, Zoller H, Tilg H, Gnaiger E, Hautz T, Schneeberger S (2022) Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome. https://doi.org/10.1016/j.ebiom.2022.104311|
» EBioMedicine 85:104311. Open Access
Meszaros Andras T, Hofmann Julia, Buch Madita L, Cardini Benno, Dunzendorfer-Matt Theresia, Nardin Florian, Blumer Michael J, Fodor Margot, Hermann Martin, Zelger Bettina, Otarashvili Giorgi, Schartner Melanie, Weissenbacher Annemarie, Oberhuber Rupert, Resch Thomas, Troppmair Jakob, Oefner Dietmar, Zoller Heinz, Tilg Herbert, Gnaiger Erich, Hautz Theresa, Schneeberger Stefan (2022) EBioMedicine
Abstract: Reliable biomarkers for organ quality assessment during normothermic machine perfusion (NMP) are desired. ATP (adenosine triphosphate) production by oxidative phosphorylation plays a crucial role in the bioenergetic homeostasis of the liver. Thus, detailed analysis of the aerobic mitochondrial performance may serve as predictive tool towards the outcome after liver transplantation.
In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24 h. Biopsy and perfusate samples were collected at the end of cold storage, at 1 h, 6 h, end of NMP, and 1 h after reperfusion. Mitochondrial function and integrity were characterized by high-resolution respirometry (HRR), AMP, ADP, ATP and glutamate dehydrogenase analysis and correlated with the clinical outcome (L-GrAFT score). Real-time confocal microscopy was performed to assess tissue viability. Structural damage was investigated by histology, immunohistochemistry and transmission electron microscopy.
A considerable variability in tissue viability and mitochondrial respiration between individual livers at the end of cold storage was observed. During NMP, mitochondrial respiration with succinate and tissue viability remained stable. In the multivariate analysis of the 35 transplanted livers (15 were discarded), area under the curve (AUC) of LEAK respiration, cytochrome c control efficiency (mitochondrial outer membrane damage), and efficacy of the mitochondrial ATP production during the first 6 h of NMP correlated with L-GrAFT.
Bioenergetic competence during NMP plays a pivotal role in addition to tissue injury markers. The AUC for markers of outer mitochondrial membrane damage, ATP synthesis efficiency and dissipative respiration (LEAK) predict the clinical outcome upon liver transplantation. • Keywords: Liver Transplantation, Normothermic machine perfusion, Mitochondria, High-resolution respirometry • Bioblast editor: Plangger M • O2k-Network Lab: AT Innsbruck Schneeberger S, AT Innsbruck Gnaiger E, AT Innsbruck Oroboros
Labels: MiParea: Respiration
Organism: Human Tissue;cell: Liver Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k