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Am J Physiol Regul Integr Comp Physiol. 2015 Jun 15;308(12):R1034-44. doi: 10.1152/ajpregu.00030.2015. Epub 2015 Apr 15.

Early hemorrhage triggers metabolic responses that build up during prolonged shock.

Author information

1
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado; angelo.dalessandro@ucdenver.edu.
2
Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
3
Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado; Department of Surgery, Denver Health Medical Center, Denver, Colorado;
4
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado;
5
Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado; and Research Laboratory, Bonfils Blood Center, Denver, Colorado.

Abstract

Metabolic staging after trauma/hemorrhagic shock is a key driver of acidosis and directly relates to hypothermia and coagulopathy. Metabolic responses to trauma/hemorrhagic shock have been assayed through classic biochemical approaches or NMR, thereby lacking a comprehensive overview of the dynamic metabolic changes occurring after shock. Sprague-Dawley rats underwent progressive hemorrhage and shock. Baseline and postshock blood was collected, and late hyperfibrinolysis was assessed (LY30 >3%) in all of the tested rats. Extreme and intermediate time points were collected to assay the dynamic changes of the plasma metabolome via ultra-high performance liquid chromatography-mass spectrometry. Sham controls were used to determine whether metabolic changes could be primarily attributable to anesthesia and supine positioning. Early hemorrhage-triggered metabolic changes that built up progressively and became significant during sustained hemorrhagic shock. Metabolic phenotypes either resulted in immediate hypercatabolism, or late hypercatabolism, preceded by metabolic deregulation during early hemorrhage in a subset of rats. Hemorrhagic shock consistently promoted hyperglycemia, glycolysis, Krebs cycle, fatty acid, amino acid, and nitrogen metabolism (urate and polyamines), and impaired redox homeostasis. Early dynamic changes of the plasma metabolome are triggered by hemorrhage in rats. Future studies will determine whether metabolic subphenotypes observed in rats might be consistently observed in humans and pave the way for tailored resuscitative strategies.

KEYWORDS:

hemorrhagic shock; mass spectrometry; metabolomics; plasma; trauma

PMID:
25876652
PMCID:
PMC4469929
DOI:
10.1152/ajpregu.00030.2015
[Indexed for MEDLINE]
Free PMC Article

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