期刊论文详细信息
BMC Emergency Medicine
Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed
Greg Beilman3  Kristine Mulier3  Vishwesh Kulkarni2  Daniel Lexcen1  Tyrone Vincent4  Elizabeth R. Lusczek3 
[1] Medtronic Inc., 710 Medtronic Parkway NE, Minneapolis 55432, MN, USA;University of Warwick School of Engineering, Coventry, CV4 7AL, UK;Department of Surgery, University of Minnesota, 516 Delaware St. SE, Minneapolis 55455, MN, USA;Department of Electrical Engineering and Computer Science, Colorado School of Mines, 1610 Illinois St., Golden 80401, CO, USA
关键词: Hemorrhagic shock;    Networks;    Metabolomics;   
Others  :  1228163
DOI  :  10.1186/s12873-015-0038-1
 received in 2014-09-25, accepted in 2014-09-25,  发布年份 2015
【 摘 要 】

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.

【 授权许可】

   
2015 Lusczek et al.; licensee BioMed Central.

附件列表
Files Size Format View
Fig. 3. 62KB Image download
Fig. 2. 32KB Image download
Fig. 1. 30KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】
  • [1]Neligan PJ, Baranov D. Trauma and aggressive homeostasis management. Anesthesiol Clin. 2013; 31:21-39.
  • [2]Pearce FJ, Drucker WR. Glucose infusion arrests the decompensatory phase of hemorrhagic shock. J Trauma. 1987; 27:11.
  • [3]Nettelbladt CG, Alibergovic A, Ljungqvist O. Pre-stress carbohydrate solution prevents fatal outcome after hemorrhage in 24-h food-deprived rats. Nutrition. 1996; 12:10.
  • [4]Dubick MA. Current concepts in fluid resuscitation for prehospital care of combat casualties. US Army Med Dep J. 2011:18.
  • [5]Determan C, Lusczek ER, Witowski NE, Lexcen D, Mulier KE, Beilman GJ. Carbohydrate fed state alters the metabolomic response to hemorrhagic shock and resuscitation in liver. Metabolomics. 2014; 10:950-957.
  • [6]Determan C, Anderson R, Becker A, Witowski N, Lusczek E, Mulier K, Beilman GJ. Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response. PloS One. 2014; 9(6):e100088.
  • [7]Mulier KE, Greenberg JG, Beilman GJ. Hypercoagulability in porcine hemorrhagic shock is present early after trauma and resuscitation. J Surg Res. 2012; 174:e31-e35.
  • [8]Lusczek ER, Lexcen DR, Witowski NE, Mulier KE, Beilman G. Urinary metabolic network analysis in trauma, hemorrhagic shock, and resuscitation. Metabolomics. 2013; 9:223-235.
  • [9]PEARCE FJ, DRUCKER WR. Glucose infusion arrests the decompensatory phase of hemorrhagic shock. J Trauma-Injury Infect Crit Care. 1987; 27:1213-1220.
  • [10]Holcomb JB, Pusateri AE, Harris RA, Charles NC, Gomez RR, Cole JP, Beall LD, Bayer V, MacPhee MJ, Hess JR. Effect of dry fibrin sealant dressings versus gauze packing on blood loss in grade v liver injuries in resuscitated swine. J Trauma. 1999; 46:49.
  • [11]Weljie AM, Newton J, Mercier P, Carlson E, Slupsky CM. Targeted profiling: quantitative analysis of 1h nmr metabolomics data. Anal Chem. 2006; 78:4430-4442.
  • [12]Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S et al.. Hmdb: a knowledgebase for the human metabolome. Nucleic Acids Res. 2009; 37(suppl 1):603-610.
  • [13]Lexcen DR, Lusczek ER, Witowski NE, Mulier KE, Beilman GJ. Metabolomics classifies phase of care and identifies risk for mortality in a porcine model of multiple injuries and hemorrhagic shock. J Trauma Acute Care Surg. 2012; 73:147-155.
  • [14]Colling K, Iyegha U, Asghar J, Lexcen D, Lusczek E, Determan CJ, et al. Pre-injury fed state alters the physiologic response in a porcine model of hemorrhagic shock and polytrauma. Shock. 2015. Epub ahead of print.
  • [15]Iyegha UP, Witowski N, Lexcen D, Mulier K, Asghar JI, Lusczek B, Beilman GJ. Does the fed state impact outcome in polytrauma and hemorrhagic shock? J Am College Surg. 2012; 215:S52.
  • [16]Fredholm BB. Adenosine and Metabolism—A Brief Historical Note. In: Adenosine. Masino S, Boison D, editors. Springer, New York; 2013: p.3-19.
  • [17]Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate levels. Mayo Clinic Proc. 2013; 88:1127-1140.
  • [18]Smolenski RT, de Jong JW, Janssen M, Lachno DR, Zydowo MM, Tavenier M, Huizer T, Yacoub MH. Formation and breakdown of uridine in ischemic hearts of rats and humans. J Mol Cell Cardiol. 1993; 25:67-74.
  • [19]Bours M, Swennen E, Virgilio FD, Cronstein B, Dagnelie P. Adenosine 5-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Therapeut. 2006; 112:358-404.
  • [20]Laubach VE, French BA, Okusa MD. Targeting of adenosine receptors in ischemia-reperfusion injury. Expert Opin Ther Targets. 2011; 15:103-118.
  • [21]Deussen A, Ohanyan V, Jannasch A, Yin L, Chilian W. Mechanisms of metabolic coronary flow regulation. J Mol Cell Cardiol. 2012; 52:794-801.
  • [22]Barbee RW, Reynolds PS, Ward KR. Assessing shock resuscitation strategies by oxygen debt repayment. Shock. 2010; 33:113-122.
  • [23]Kruse O, Grunnet N, Barfod C. Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Scand J Trauma Resusc Emerg Med. 2011; 19:74. BioMed Central Full Text
  • [24]Jansen TC, van Bommel J, Schoonderbeek FJ, Visser SJS, van der Klooster JM, Lima AP, Willemsen SP, Bakker J. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Res Crit Care Med. 2010; 182:752-761.
  文献评价指标  
  下载次数:14次 浏览次数:5次