title: 1H-NMR metabolomic biomarkers of poor outcome after hemorrhagic shock are absent in hibernators.
abstract: BACKGROUND
  Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
  
  
  RESULTS
  Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ± 0.5 °C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
  
  
  CONCLUSIONS
  An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, United States of America; Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, United States of America.
authors.forename: Lori K
authors.initials: LK
authors.lastname: Bogren
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, United States of America.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, United States of America.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Johnston
authors.affiliation: Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Sinha
authors.affiliation: Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Serkova
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, United States of America; Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, United States of America.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Drew
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006605:Hibernation; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000517:prevention & control; D012589:Sciuridae; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008055:Lipids