title: Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed.
abstract: BACKGROUND
  Treatment with oral carbohydrate prior to trauma and hemorrhage confers a survival benefit in small animal models. The impact of fed states on survival in traumatically injured humans is unknown. This work uses regulatory networks to examine the effect of carbohydrate pre-feeding on metabolic response to polytrauma and hemorrhagic shock in a clinically-relevant large animal model.
  
  
  METHODS
  Male Yorkshire pigs were fasted overnight (n = 64). Pre-fed animals (n = 32) received an oral bolus of Karo\textregistered\syrup before sedation. All animals underwent a standardized trauma, hemorrhage, and resuscitation protocol. Serum samples were obtained at set timepoints. Proton NMR was used to identify and quantify serum metabolites. Metabolic regulatory networks were constructed from metabolite concentrations and rates of change in those concentrations to identify controlled nodes and controlling nodes of the network.
  
  
  RESULTS
  Oral carbohydrate pre-treatment was not associated with survival benefit. Six metabolites were identified as controlled nodes in both groups: adenosine, cytidine, glycerol, hypoxanthine, lactate, and uridine. Distinct groups of controlling nodes were associated with controlled nodes; however, the composition of these groups depended on feeding status.
  
  
  CONCLUSIONS
  A common metabolic output, typically associated with injury and hypoxia, results from trauma and hemorrhagic shock. However, this output is directed by different metabolic inputs depending upon the feeding status of the subject. Nodes of the network that are related to mortality can potentially be manipulated for therapeutic effect; however, these nodes differ depending upon feeding status.
authors.affiliation: Department of Surgery, University of Minnesota, 516 Delaware St. SE, Minneapolis, MN, 55455, USA. lusc0006@umn.edu.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Lusczek
authors.affiliation: Department of Electrical Engineering and Computer Science, Colorado School of Mines, 1610 Illinois St., Golden, CO, 80401, USA. tvincent@mines.edu.
authors.forename: Tyrone
authors.initials: T
authors.lastname: Vincent
authors.affiliation: Medtronic Inc., 710 Medtronic Parkway NE, Minneapolis, MN, 55432, USA. lexc0003@umn.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lexcen
authors.affiliation: University of Warwick School of Engineering, CV4 7AL, Coventry, UK. V.Kulkarni@warwick.ac.uk.
authors.forename: Vishwesh
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Department of Surgery, University of Minnesota, 516 Delaware St. SE, Minneapolis, MN, 55455, USA. groeh001@umn.edu.
authors.forename: Kristine
authors.initials: K
authors.lastname: Mulier
authors.affiliation: Department of Surgery, University of Minnesota, 516 Delaware St. SE, Minneapolis, MN, 55455, USA. beilm001@umn.edu.
authors.forename: Greg
authors.initials: G
authors.lastname: Beilman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D004040:Dietary Carbohydrates; D005247:Feeding Behavior; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D009104:Multiple Trauma / Q000378:metabolism* / Q000401:mortality; D018384:Oxidative Stress; D011897:Random Allocation; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000401:mortality; D013552:Swine
chemical_list: D015415:Biomarkers; D004040:Dietary Carbohydrates