Metabolomic profiles of tissues could greatly contribute to advancements in personalized medicine but are influenced by differences in adopted preanalytical procedures; nonhomogeneous pre- and post-excision ischemia times are potential sources of variability. In this study, we monitored the impact of ischemia on the metabolic profiles, acquired with high-resolution magic-angle-spinning 1H NMR, of 162 human liver samples collected during and up to 6 h after routine surgery. The profiles changed significantly as a function of intraoperative warm ischemia (WI) and postresection cold ischemia (CI) time, with significant variations in the concentration of the same 16 metabolites. Therefore, a tight control of the preanalytical phase is essential for reliable metabolomic analyses of liver diseases. The NMR profiles provide a reliable "fingerprint" of ischemia and have predictive value: the best-performing predictive models are found to discriminate extreme time points of CI (0′ vs 360 ′) in the training set with cross-validation accuracy of ∼90%; samples in the validation cohort can discriminate short (≤60′) from long (≥180′) CI with an accuracy of ∼80%. For WI, the corresponding figures are 95.6 and 92%, respectively. Therefore, ischemia NMR profiles might become a tool for tissue quality control in biobanks.

HR-MAS, ischemia, liver, NMR, preanalytics, tissue metabolomics,
Journal of Proteome Research
Department of Pathology

Cacciatore, S, Hu, X, Viertler, C, Kap, Y.S, Bernhardt, G.A, Mischinger, H.-J, … Turano, P. (2013). Effects of intra- and post-operative ischemia on the metabolic profile of clinical liver tissue specimens monitored by NMR. Journal of Proteome Research, 12(12), 5723–5729. doi:10.1021/pr400702d