A four-compartment metabolomics analysis of the liver, muscle, serum, and urine response to polytrauma with hemorrhagic shock following carbohydrate prefeed

PLoS One. 2015 Apr 14;10(4):e0124467. doi: 10.1371/journal.pone.0124467. eCollection 2015.

Abstract

Objective: Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

Methods: Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

Results: Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

Conclusions: Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Discriminant Analysis
  • Disease Models, Animal
  • Glucose / analysis
  • Glucose / metabolism*
  • Least-Squares Analysis
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Metabolomics*
  • Multiple Trauma / complications*
  • Multiple Trauma / metabolism
  • Muscles / metabolism*
  • Resuscitation
  • Shock, Hemorrhagic / complications*
  • Shock, Hemorrhagic / metabolism
  • Swine

Substances

  • Glucose

Grants and funding

Funding was provided by Office of Naval Research - N00014-09-0323, University of Minnesota, and North Memorial Center. Funding for NMR instrumentation was provided by the Office of the Vice President for Research, the Medical School, the College of Biological Science, National Institutes of Health, NSF, and the Minnesota Medical Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.