title: Early hemorrhage triggers metabolic responses that build up during prolonged shock.
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.
authors: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado; angelo.dalessandro@ucdenver.edu.
authors: Angelo
authors: A
authors: D'Alessandro
authors: Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
authors: Hunter B
authors: HB
authors: Moore
authors: 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;
authors: Ernest E
authors: EE
authors: Moore
authors: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado;
authors: Matthew
authors: M
authors: Wither
authors: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado;
authors: Travis
authors: T
authors: Nemkov
authors: Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
authors: Eduardo
authors: E
authors: Gonzalez
authors: Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
authors: Anne
authors: A
authors: Slaughter
authors: Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
authors: Miguel
authors: M
authors: Fragoso
authors: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, South, Aurora, Colorado;
authors: Kirk C
authors: KC
authors: Hansen
authors: Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado; and Research Laboratory, Bonfils Blood Center, Denver, Colorado.
authors: Christopher C
authors: CC
authors: Silliman
authors: Department of Surgery/Trauma Research Center, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado;
authors: Anirban
authors: A
authors: Banerjee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001810:Blood Volume; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004734:Energy Metabolism; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: hemorrhagic shock; mass spectrometry; metabolomics; plasma; trauma