A Metabolomic Approach to the Pathogenesis of Ventilator-induced Lung Injury

• Published in: Anesthesiology (Philadelphia) 2014-03, Vol.120 (3), p.694-702
• Main Authors: Izquierdo-García, José L, Naz, Shama, Nin, Nicolás, Rojas, Yeny, Erazo, Marcela, Martínez-Caro, Leticia, García, Antonia, de Paula, Marta, Fernández-Segoviano, Pilar, Casals, Cristina, Esteban, Andrés, Ruíz-Cabello, Jesús, Barbas, Coral, Lorente, José A
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Biomarkers - blood; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid - methods; Disease Models, Animal; Least-Squares Analysis; Lung - metabolism; Lung - pathology; Magnetic Resonance Spectroscopy - methods; Male; Mass Spectrometry - methods; Medical sciences; Metabolomics - methods; Pilot Projects; Positive-Pressure Respiration - methods; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Respiration, Artificial - adverse effects; Tidal Volume - physiology; Ventilator-Induced Lung Injury - blood; Ventilator-Induced Lung Injury - metabolism; Ventilator-Induced Lung Injury - pathology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000000074

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 htidal 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