Metabolomics profiling reveals different patterns in an animal model of asphyxial and dysrhythmic cardiac arrest

Abstract

Cardiac arrest (CA) is not a uniform condition and its pathophysiology strongly depends on its cause. In this work we have used a metabolomics approach to study the dynamic metabolic changes occurring in the plasma samples of a swine model following two different causes of CA, namely asphyxia (ACA) and ventricular fibrillation (VFCA). Plasma samples were collected at baseline and every minute during the experimental phases. In order to identify the metabolomics profiles characterizing the two pathological entities, all samples were analysed by 1H NMR spectroscopy and LC-MS/MS spectrometry.The metabolomics fingerprints of ACA and VFCA significantly differed during the peri-arrest period and the resuscitation phase. Major alterations were observed in plasma concentrations of metabolites related to tricarboxylic acid (TCA) cycle, urea cycle, and anaplerotic replenishing of TCA. ACA animals showed significant metabolic disturbances during the asphyxial and CA phases, while for VFCA animals this phenomenon resulted shifted at the resuscitation phase. Interestingly, starting from the asphyxial phase, the ACA animals were stratified in two groups based on their metabolomics profiles that resulted to be correlated with the clinical outcome. Succinate overproduction was observed in the animals with the worse outcome, suggesting a potential prognostic role for this metabolite.

Forensic NMR metabolomics: one more arrow in the quiver

“…Notwithstanding the growing use of NMR metabolomics in various fields of forensic science, its potential in the forensic pathology scenario has not been completely exploited. A very recent work published in the literature opens the way for differential diagnosis of asphyxial deaths (Varvarousis et al 2017 ) suggesting that more efforts should be also made in this field.…”

Exploring Perinatal Asphyxia by Metabolomics

“…In an anoxic-hypoxic milieu, fumarate acts as an electron acceptor and it is reduced to succinate by the reverse activity of succinate dehydrogenase, causing the accumulation of this metabolite, with α-ketoglutarate dehydrogenase being the limiting enzyme in this mitochondrial safeguard mechanism. The usefulness of succinate as marker of hypoxia-ischemia in circulating biofluids is limited by the high degree of inter-individual variability recently described in an animal model [56] and by the very short half-life of succinate in blood (with an average 5-min re-oxygenation time after a severe ischemic-hypoxic insult being sufficient to restore the baseline values in blood and in the ischemic heart) [57].…”

Quantitative analysis, pharmacokinetics and metabolomics study for the comprehensive characterization of the salt-processing mechanism of Psoraleae Fructus

“…The consequent “bucket table” was then imported to SIMCA-P software (version 13.0, Umetrics AB) for multivariate statistical analysis. PCA was first performed as the unsupervised method for outlier identification 35 . Subsequently, the OPLS-DA was implemented as the supervised method to identify potential biomarkers.…”