1H-NMR Metabolomics Identifies Significant Changes in Metabolism over Time in a Porcine Model of Severe Burn and Smoke Inhalation.

Abstract

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (1H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using 1H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time (p < 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury.