1H‐NMR metabolomic biomarkers of poor outcome after hemorrhagic shock are absent in hibernators (590.1)

Abstract

Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS, systemic ischemia is followed by reperfusion during medical intervention (I/R) resulting in a disruption of cellular metabolic processes and ultimate tissue and organ dysfunction. Resistance to I/R injury is a characteristic of hibernating mammals. The present study examined if arctic ground squirrels (AGS) are protected from warm HS‐induced global I/R injury due to the ability to maintain a stable metabolic homeostasis during HS. Rats and AGS were subject to HS by withdrawing blood to maintain a MAP of 35 mmHg for 20 min before reperfusion. Body temperature was maintained at 37±0.5°C. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion and were then analyzed via 1H‐NMR spectroscopy for hydrophilic and lipophilic metabolites. Rats had a qualitative shift in their hydrophilic metabolic fingerprint and had alterations in several metabolites (acetate, alanine, glutamine, histidine, β‐hydroxybutyrate, lactate, lysine, and tyrosine ) during I/R indicative of metabolic shut‐down and organ damage. In contrast, AGS, regardless of season, were able to maintain a qualitative 1H‐NMR metabolic homeostasis with little (winter) or no (summer) changes in quantified metabolites during HS‐induced global I/R. In conclusion, AGS are resistant to disruptions in their metabolic processes and organ damage during warm HS‐ I/R.Grant Funding Source: Supported by USAMRMC W81XWH009‐2‐0134