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 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.
Hrydziuszko
Olga
O
Centre for Systems Biology, University of Birmingham, Birmingham, United Kingdom.
Silva
Michael A
MA
Perera
M Thamara P R
MT
Richards
Douglas A
DA
Murphy
Nick
N
Mirza
Darius
D
Viant
Mark R
MR
D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D017551:Microdialysis; D008875:Middle Aged; D025341:Principal Component Analysis