1H-NMR Metabolomics Characterizes Transition From Ebb To Flow In A Porcine Model Of Smoke Inhalation And Severe Burn Injury

Abstract

Burn injury initiates a metabolic response that, even when treated, causes muscle wasting and organ dysfunction in burn patients as long as two years following injury. This increased metabolic rate, termed “flow” phase in burn physiology, is initially masked by low blood pressure and inadequate oxygen supply in burn shock, known as “ebb” phase. Our study examined the metabolic transition between the “ebb” and “flow” phases of burn recovery using proton nuclear magnetic resonance (1H-NMR) spectroscopy in a porcine model of severe burn injury with additional smoke inhalation. We hypothesized the serum metabolomes of porcine subjects would be distinguishable by time point, and the changes in individual metabolite concentrations would characterize the shift from “ebb” to “flow” in burn physiology. Fifteen pigs received 40% total body surface area (TBSA) thermal burns with additional pine bark smoke inhalation treatment. Subjects were resuscitated and kept anesthetized until 72 hours post-burn or death. Arterial blood samples were drawn at baseline (pre-burn) and every 24 hours until 72 hours post-injury or death. The aqueous portion of each sample was analyzed in a 700MHz spectrometer and metabolite peaks were fit to spectra using Chenomx software. Thirty-eight metabolites were detected in 39 samples, and principal component analysis (PCA) was conducted to separate samples by time point. 51.6% of metabolite variability was captured in the first two principal components. We found post-burn metabolomes of porcine subjects to be distinguishable by time point using 1H-NMR and principal component analysis. We also constructed a framework for non-lactic acidosis in resuscitated burn subjects that emphasized oxidative stress and increased fatty acid catabolism as root causes of organic acid accumulation. Further studies will be required to confirm and elaborate on the post-burn metabolic pathways suggested by this analysis.