Metabolic profiling during ex vivo machine perfusion of the human liver View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04

AUTHORS

Bote G Bruinsma, Gautham V Sridharan, Pepijn D Weeder, James H Avruch, Nima Saeidi, Sinan Özer, Sharon Geerts, Robert J Porte, Michal Heger, Thomas M van Gulik, Paulo N Martins, James F Markmann, Heidi Yeh, Korkut Uygun

ABSTRACT

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 °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. More... »

PAGES

22415

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep22415

DOI

http://dx.doi.org/10.1038/srep22415

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028545325

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26935866


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