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

Dimitrios Varvarousis,Fabio De-Giorgio,Theodoros Xanthos,Emanuela Locci,Nicoletta Iacovidou,Paola Scano,Matteo Stocchero,Paolo Mura,Gabriele Finco,Massimo Mura,Antonio Noto,Chryssoula Staikou,Giulio Ferino,Alfonso Baldi,Apostolos Papalois,Athanasios Chalkias,Ernesto D’Aloja

doi:10.1038/s41598-017-16857-6

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.

Highlights

Cardiac arrest (CA) is not a uniform condition and its pathophysiology strongly depends on its cause
In the asphyxial CA (ACA) group, during asphyxia, mean arterial pressure (MAP) of animals showed a significant drop after the 4th minute (p-value < 0.005)
At the beginning of cardiopulmonary resuscitation (CPR) our study identified a further increase of lactate, succinate, malate, glutamate, and in a less evident way of alanine (p-value = 0.08) in the plasma of ACA animals when compared to VFCA (Supplementary Table S2)

Summary

Introduction

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). The metabolomics fingerprints of ACA and VFCA significantly differed during the peri-arrest period and the resuscitation phase. Evidence suggests that asphyxial CA (ACA) differs significantly from primary CA of cardiac origin (dysrhythmic) with regard to pathophysiological mechanisms, tissue damage, post-resuscitation organ dysfunction, and response to therapy[3]. Plasma metabolite concentration changes provide useful information, as they are the closest link to cellular metabolism in the whole body and to its disturbances following CA and/or resuscitation. Identifying specific plasma metabolite changes, associated with responses either to asphyxial or dysrhythmic CA, may represent a feasible tool to achieve an earlier diagnosis and a more accurate prognosis

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Conclusion