Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

To improve the outcome of orthotopic liver transplantation (OLT), knowledge of early molecular events occurring upon ischemia/reperfusion is essential. Powerful approaches for profiling metabolic changes in tissues and biofluids are now available. Our objective was to investigate the applicability o...

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Veröffentlicht in:Omics (Larchmont, N.Y.) N.Y.), 2010-04, Vol.14 (2), p.143-150
Hauptverfasser: Hrydziuszko, Olga, Silva, Michael A., P. R. Perera, M. Thamara, Richards, Douglas A., Murphy, Nick, Mirza, Darius, Viant, Mark R.
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Sprache:eng
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Zusammenfassung:To improve the outcome of orthotopic liver transplantation (OLT), knowledge of early molecular events occurring upon ischemia/reperfusion is essential. Powerful approaches for profiling metabolic changes in tissues and biofluids are now available. Our objective was to investigate the applicability of two technologies to a small but well-defined cohort of patients undergoing OLT: consecutive liver biopsies by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and microdialysates of extracellular fluid by coulometric electrochemical array detection (CEAD). FT-ICR MS detected reproducibly more than 4,000 peaks, revealing hundreds of significant metabolic differences between pre- and postreperfusion grafts. These included increased urea production, bile acid synthesis and clearance of preservation solution upon reperfusion, indicating a rapid resumption of biochemical function within the graft. FT-ICR MS also identified successfully the only graft obtained by donation-after-cardiac-death as a “metabolic outlier.” CEAD time–profile analysis showed that there was considerable change in redox-active metabolites (up to 18 h postreperfusion), followed by their stabilization. Collectively these results verify the applicability of FT-ICR MS and CEAD for characterizing multiple metabolic pathways during OLT. The success of this proof-of-principle application of these technologies to a clinical setting, considering the potential metabolic heterogeneity across only eight donor livers, is encouraging.
ISSN:1536-2310
1557-8100
DOI:10.1089/omi.2009.0139