Transplant Division, Department of Surgery
Analytical, Diagnostic and Therapeutic Techniques and Equipment | Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Computational Biology | Digestive System | Hepatology | Surgery
As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 degrees C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from 'transplantable' DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
donor livers, functional machine perfusion, transplanation, metabolomics, donation after circulatory death
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Copyright © 2016, Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
DOI of Published Version
Sci Rep. 2016 Mar 3;6:22415. doi: 10.1038/srep22415. Link to article on publisher's site
Bruinsma, Bote G.; Sridharan, Gautham V.; Weeder, Pepijn D.; Avruch, James H.; Saeidi, Nima; Ozer, Sinan; Geerts, Sharon; Porte, Robert J.; Heger, Michal; van Gulik, Thomas M.; Martins, Paulo N.A.; Markmann, James F.; Yeh, Heidi; and Uygun, Korkut, "Metabolic profiling during ex vivo machine perfusion of the human liver" (2016). Surgery Publications and Presentations. 156.
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This work is licensed under a Creative Commons Attribution 4.0 License.
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