title: A Metabolomic Approach to the Pathogenesis of Ventilator-induced Lung Injury.
abstract: BACKGROUND
  Global metabolic profiling using quantitative nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) is useful for biomarker discovery. The objective of this study was to discover biomarkers of acute lung injury induced by mechanical ventilation (ventilator-induced lung injury [VILI]), by using MRS and MS.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to two ventilatory strategies for 2.5 h: tidal volume 9 ml/kg, positive end-expiratory pressure 5 cm H2O (control, n = 14); and tidal volume 25 ml/kg and positive end-expiratory pressure 0 cm H2O (VILI, n = 10). Lung tissue, bronchoalveolar lavage fluid, and serum spectra were obtained by high-resolution magic angle spinning and H-MRS. Serum spectra were acquired by high-performance liquid chromatography coupled to quadupole-time of flight MS. Principal component and partial least squares analyses were performed.
  
  
  RESULTS
  Metabolic profiling discriminated characteristics between control and VILI animals. As compared with the controls, animals with VILI showed by MRS higher concentrations of lactate and lower concentration of glucose and glycine in lung tissue, accompanied by increased levels of glucose, lactate, acetate, 3-hydroxybutyrate, and creatine in bronchoalveolar lavage fluid. In serum, increased levels of phosphatidylcholine, oleamide, sphinganine, hexadecenal and lysine, and decreased levels of lyso-phosphatidylcholine and sphingosine were identified by MS.
  
  
  CONCLUSIONS
  This pilot study suggests that VILI is characterized by a particular metabolic profile that can be identified by MRS and MS. The metabolic profile, though preliminary and pending confirmation in larger data sets, suggests alterations in energy and membrane lipids.SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT.
authors.affiliation: From the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain (J.L.I.-G., N.N., Y.R., L.M.-C., M.d.P., P.F.-S., C.C., A.E., J.R.-C., and J.A.L.); Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (J.L.I.-G. and J.R.-C.); Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain (S.N., M.E., A.G., and C.B.); Hospital Universitario de Torrejón, Madrid, Spain (N.N.); Department of Critical Care, Hospital Universitario de Getafe, Madrid, Spain (Y.R., L.M.-C., M.d.P., P.F.-S., A.E., and J.A.L.); Universidad Complutense de Madrid, Madrid, Spain (C.C. and J.R.-C.); and Universidad Europea de Madrid, Madrid, Spain (J.A.L.).
authors.forename: José L
authors.initials: JL
authors.lastname: Izquierdo-García
authors.forename: Shama
authors.initials: S
authors.lastname: Naz
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.forename: Yeny
authors.initials: Y
authors.lastname: Rojas
authors.forename: Marcela
authors.initials: M
authors.lastname: Erazo
authors.forename: Leticia
authors.initials: L
authors.lastname: Martínez-Caro
authors.forename: Antonia
authors.initials: A
authors.lastname: García
authors.forename: Marta
authors.initials: M
authors.lastname: de Paula
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.forename: Cristina
authors.initials: C
authors.lastname: Casals
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruíz-Cabello
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D016018:Least-Squares Analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D011175:Positive-Pressure Respiration / Q000379:methods; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects; D013990:Tidal Volume / Q000502:physiology; D055397:Ventilator-Induced Lung Injury / Q000097:blood / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers