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- Title
A metabolomic approach for diagnosis of experimental sepsis.
- Authors
Izquierdo-García, José; Nin, Nicolás; Ruíz-Cabello, Jesús; Rojas, Yeny; Paula, Marta; López-Cuenca, Sonia; Morales, Luis; Martínez-Caro, Leticia; Fernández-Segoviano, Pilar; Esteban, Andrés; Lorente, José; Izquierdo-García, José L; Nin, Nicolás; Ruíz-Cabello, Jesús; de Paula, Marta; López-Cuenca, Sonia; Martínez-Caro, Leticia; Fernández-Segoviano, Pilar; Esteban, Andrés; Lorente, José A
- Abstract
<bold>Background: </bold>The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis.<bold>Objective: </bold>To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis.<bold>Methods: </bold>Male Sprague-Dawley rats (weight 325-375 g) underwent cecal ligation and puncture (n = 14, septic group) or sham procedure (n = 14, control group) and 24 h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for (1)H NMR and high-resolution magic-angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis.<bold>Results: </bold>NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%.<bold>Conclusions: </bold>NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis.
- Subjects
SEPSIS; BIOMARKERS; NUCLEAR magnetic resonance; METABOLITES; SPECTRUM analysis; CHEMOMETRICS; DIAGNOSIS
- Publication
Intensive Care Medicine, 2011, Vol 37, Issue 12, p2023
- ISSN
0342-4642
- Publication type
journal article
- DOI
10.1007/s00134-011-2359-1