Urinary metabolic network analysis in trauma, hemorrhagic shock, and resuscitation
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Hemorrhagic shock, often a result of traumatic injury, is a condition of reduced perfusion that results in diminished delivery of oxygen to tissues. The disruption in oxygen delivery induced by both ischemia (diminished oxygen delivery) and reperfusion (restoration of oxygen delivery) has profound consequences for cellular metabolism and the maintenance of homeostasis. The pathophysiologic state associated with traumatic injury and hemorrhagic shock was studied with a scale-invariant metabolic network. Urinary metabolic profiles were constructed from NMR spectra of urine samples collected at set timepoints in a porcine model of hemorrhagic shock that included a pulmonary contusion, a liver crush injury, and a 35 % controlled bleed. The network was constructed from these metabolic profiles. A partial least squares discriminant analysis (PLS-DA) model that discriminates by experimental timepoint was also constructed. Comparisons of the network (functional relationships among metabolites) and PLS-DA model (observable relationships to experimental time course) revealed complementary information. First, ischemia/reperfusion injury and evidence of cell death due to hemorrhage was associated with early resuscitation timepoints. Second, evidence of increased protein catabolism and traumatic injury was associated with late resuscitation timepoints. These results are concordant with generally accepted views of the metabolic progression of shock.
KeywordsUrine Metabolomics Metabolic networks NMR Hemorrhagic shock
The authors wish to thank the Office of Naval Research for their continued funding of this research (grants N00014-09-1-0323 and N000-05-1-0344), the Minnesota Supercomputing Institute, the University of Minnesota’s Nuclear Magnetic Resonance Facility (funding provided by NSF grant BIR-961477, the University of Minnesota Medical School, and the Minnesota Medical Foundation), and the University of Minnesota. The authors also wish to thank Dr. Susan Jones for her helpful feedback in the preparation of this manuscript.
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