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

2010; Mary Ann Liebert, Inc.; Volume: 14; Issue: 2 Linguagem: Inglês

10.1089/omi.2009.0139

1557-8100

Olga Hrydziuszko, Michael A. Silva, M. Thamara P. R. Perera, Douglas A. Richards, Nick Murphy, Darius F. Mirza, Mark R. Viant,

Liver Disease and Transplantation

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.