Liver metabolomic changes identify biochemical pathways in hemorrhagic shock.
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.


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 ((1)H) and phosphorous ((31)P) 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 (1)H and (31)P 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.
Scribner
Drew M
DM
Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
Witowski
Nancy E
NE
Mulier
Kristine E
KE
Lusczek
Elizabeth R
ER
Wasiluk
Karen R
KR
Beilman
Greg J
GJ
D015308:Anaerobic Threshold / Q000502:physiology; D000818:Animals; D005943:Gluconeogenesis / Q000502:physiology; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000502:physiology*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010759:Phosphorus Isotopes; D011522:Protons; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy; D034421:Sus scrofa; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D010714:Phosphatidylethanolamines; D010759:Phosphorus Isotopes; D011522:Protons; C002449:glycerophosphoethanolamine; D005997:Glycerylphosphorylcholine; D010728:Phosphoenolpyruvate; D014532:Uridine Diphosphate Glucose