Effects of intra- and post-operative ischemia on the metabolic profile of clinical liver tissue specimens monitored by NMR

J Proteome Res. 2013 Dec 6;12(12):5723-9. doi: 10.1021/pr400702d. Epub 2013 Oct 29.


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 (1)H 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.

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / secondary
  • Carcinoma / surgery
  • Cold Ischemia
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • Humans
  • Liver / metabolism*
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Magnetic Resonance Spectroscopy
  • Metabolome*
  • Models, Statistical
  • Time Factors
  • Warm Ischemia


  • Biomarkers