Liver metabolomic changes identify biochemical pathways in hemorrhagic shock

Drew M. Scribner, Nancy E. Witowski, Kristine E. Mulier, Elizabeth R. Lusczek, Karen R. Wasiluk, Greg J. Beilman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Despite ongoing advances in treatment, thousands of patients still die annually from complications due to hemorrhagic shock, a condition causing dramatic physiologic and metabolic changes as cells switch to anaerobic metabolism in response to oxygen deprivation. As the shift from aerobic to anaerobic metabolism occurs in the peripheral tissues during shock, the liver must increase production of endogenous glucose as well as process excess lactate produced in the periphery. This places the liver at the center of metabolic regulation in the body during hemorrhagic shock. Therefore, we hypothesized that liver tissue from pigs during an in vivo model of hemorrhagic shock (n = 6) would reflect resultant metabolic changes. Materials and Methods: The in vivo model of shock consisted of 45 min of shock followed by 8 h of hypotensive resuscitation (80 mmHg) and subsequent normotensive resuscitation (90 mmHg) ending 48 h after the shock period. Control groups of pigs (n = 3) (1) shock with no resuscitation, and (2) only anesthesia and instrumentation, also were included. Metabolic changes within the liver after shock and during resuscitation were investigated using both proton (1H) and phosphorous (31P) nuclear magnetic resonance (NMR) spectroscopy. Results: Concentrations of glycerylphosphorylcholine (GPC) and glycerylphosphorylethanolamine (GPE) were significantly lower at 8 h after shock, with recovery to baseline by 23 and 48 h after shock. Uridine diphosphate-glucose (UDP-glucose), and phosphoenolpyruvate (PEP) were elevated 23 h after shock. Conclusions: These results indicate that 1H and 31P NMR spectroscopy can be used to identify differences in liver metabolites in an in vivo model of hemorrhagic shock, indicating that metabolomic analysis can be used to elucidate biochemical events occurring during this complex disease process.

Original languageEnglish (US)
Pages (from-to)e131-e139
JournalJournal of Surgical Research
Volume164
Issue number1
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
The authors thank the staff of Experimental Surgical Services, University of Minnesota, for their excellent technical expertise and assistance during the in vivo studies, and Dr. Beverly Ostrowski and the staff at the NMR facility, University of Minnesota, for their help not only in using the NMR spectrometers, but for help with NMR data analysis. This work was supported in part by grant N00014-05-1-0344 from the United States Department of Defense , Navy, Washington, DC.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • UDP-glucose, phosphoenolpyruvate
  • anaerobic metabolism
  • gluconeogenesis
  • glycerylphosphorylcholine
  • glycerylphosphorylethanolamine
  • nuclear magnetic resonance spectroscopy

Fingerprint

Dive into the research topics of 'Liver metabolomic changes identify biochemical pathways in hemorrhagic shock'. Together they form a unique fingerprint.

Cite this