title: Effects of intra- and post-operative ischemia on the metabolic profile of clinical liver tissue specimens monitored by NMR.
abstract: 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.
authors.affiliation: CERM, University of Florence , Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacciatore
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.forename: Christian
authors.initials: C
authors.lastname: Viertler
authors.forename: Marcel
authors.initials: M
authors.lastname: Kap
authors.forename: Gerwin A
authors.initials: GA
authors.lastname: Bernhardt
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Mischinger
authors.forename: Peter
authors.initials: P
authors.lastname: Riegman
authors.forename: Kurt
authors.initials: K
authors.lastname: Zatloukal
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Paola
authors.initials: P
authors.lastname: Turano
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D050377:Cold Ischemia; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D015233:Models, Statistical; D013997:Time Factors; D052096:Warm Ischemia
chemical_list: D015415:Biomarkers