Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context
Summary: Background: 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 aerob...
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Elsevier
2022-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422004935 |
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| author | Andras T. Meszaros Julia Hofmann Madita L. Buch Benno Cardini Theresia Dunzendorfer-Matt Florian Nardin Michael J. Blumer Margot Fodor Martin Hermann Bettina Zelger Giorgi Otarashvili Melanie Schartner Annemarie Weissenbacher Rupert Oberhuber Thomas Resch Jakob Troppmair Dietmar ..fner Heinz Zoller Herbert Tilg Erich Gnaiger Theresa Hautz Stefan Schneeberger |
| author_facet | Andras T. Meszaros Julia Hofmann Madita L. Buch Benno Cardini Theresia Dunzendorfer-Matt Florian Nardin Michael J. Blumer Margot Fodor Martin Hermann Bettina Zelger Giorgi Otarashvili Melanie Schartner Annemarie Weissenbacher Rupert Oberhuber Thomas Resch Jakob Troppmair Dietmar ..fner Heinz Zoller Herbert Tilg Erich Gnaiger Theresa Hautz Stefan Schneeberger |
| author_sort | Andras T. Meszaros |
| collection | DOAJ |
| description | Summary: Background: 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. Methods: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh 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. Findings: 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.ßh of NMP correlated with L-GrAFT. Interpretations: 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. Funding: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH. |
| first_indexed | 2024-04-12T10:40:45Z |
| format | Article |
| id | doaj.art-e529ae879efe4ad79d300a1b0ac02665 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-12T10:40:45Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-e529ae879efe4ad79d300a1b0ac026652022-12-22T03:36:37ZengElsevierEBioMedicine2352-39642022-11-0185104311Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in contextAndras T. Meszaros0Julia Hofmann1Madita L. Buch2Benno Cardini3Theresia Dunzendorfer-Matt4Florian Nardin5Michael J. Blumer6Margot Fodor7Martin Hermann8Bettina Zelger9Giorgi Otarashvili10Melanie Schartner11Annemarie Weissenbacher12Rupert Oberhuber13Thomas Resch14Jakob Troppmair15Dietmar ..fner16Heinz Zoller17Herbert Tilg18Erich Gnaiger19Theresa Hautz20Stefan Schneeberger21Department of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria; Department of Anatomy, Histology and Embryology, Division of Clinical and Functional Anatomy, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Anatomy, Histology and Embryology, Division of Clinical and Functional Anatomy, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine I, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine I, Medical University of Innsbruck, Innsbruck, AustriaOroboros Instruments, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, organLife... Laboratory and Daniel Swarovski Research Laboratory, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria; Corresponding author. Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.Summary: Background: 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. Methods: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh 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. Findings: 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.ßh of NMP correlated with L-GrAFT. Interpretations: 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. Funding: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH.http://www.sciencedirect.com/science/article/pii/S2352396422004935LiverTransplantationNormothermic machine perfusionMitochondriaHigh-resolution respirometry |
| spellingShingle | Andras T. Meszaros Julia Hofmann Madita L. Buch Benno Cardini Theresia Dunzendorfer-Matt Florian Nardin Michael J. Blumer Margot Fodor Martin Hermann Bettina Zelger Giorgi Otarashvili Melanie Schartner Annemarie Weissenbacher Rupert Oberhuber Thomas Resch Jakob Troppmair Dietmar ..fner Heinz Zoller Herbert Tilg Erich Gnaiger Theresa Hautz Stefan Schneeberger Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context EBioMedicine Liver Transplantation Normothermic machine perfusion Mitochondria High-resolution respirometry |
| title | Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context |
| title_full | Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context |
| title_fullStr | Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context |
| title_full_unstemmed | Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context |
| title_short | Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context |
| title_sort | mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeresearch in context |
| topic | Liver Transplantation Normothermic machine perfusion Mitochondria High-resolution respirometry |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422004935 |
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