SCIENTIfIC REPORtS | 7: 16575 | DOI:10.1038/s41598-017-16857-6
reveals dierent patterns in an
animal model of asphyxial and
dysrhythmic cardiac arrest
, Theodoros Xanthos
, Giulio Ferino
, Antonio Noto
, Nicoletta Iacovidou
, Paola Scano
, Athanasios Chalkias
, Apostolos Papalois
, Fabio De-Giorgio
, Paolo Mura
, Chryssoula Staikou
, Matteo Stocchero
, Gabriele Finco
& Emanuela Locci
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 dierent causes of CA, namely asphyxia (ACA)
and ventricular brillation (VFCA). Plasma samples were collected at baseline and every minute
during the experimental phases. In order to identify the metabolomics proles characterizing the two
pathological entities, all samples were analysed by
H NMR spectroscopy and LC-MS/MS spectrometry.
The metabolomics ngerprints of ACA and VFCA signicantly diered 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 signicant 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 stratied in two groups based on their metabolomics proles 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.
Cardiac arrest (CA) is a leading cause of death worldwide, affecting over 350,000 individuals every year
However, CA is not a uniform condition and its pathophysiology strongly depends on the underlying cause.
Asphyxial and cardiac causes count for the vast majority of CA. Evidence suggests that asphyxial CA (ACA)
diers signicantly from primary CA of cardiac origin (dysrhythmic) with regard to pathophysiological mech-
anisms, tissue damage, post-resuscitation organ dysfunction, and response to therapy
. ACA is characterized
by a prolonged preceding period where hypoxia and acidosis progressively advance along with gradually dete-
riorating cardiopulmonary function until CA. On the contrary, dysrhythmic CA due to ventricular brillation
(VF) or ventricular tachycardia (VT) leads to sudden and complete cessation of blood ow. Despite the impor-
tant advances in our understanding of CA and cardiopulmonary resuscitation (CPR) over the last decades, the
Medical School, National and Kapodistrian University of Athens, Athens, Greece.
European University Cyprus,
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
diseases Laboratory, Children Hospital “A. Cao”, Cagliari, Italy.
Department of Surgical Sciences, University
of Cagliari, Cagliari, Italy.
Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy.
Institute for the Study of
Macromolecules, ISMAC, National Council of Research, Lab, NMR, Milan, Italy.
Hellenic Society of Cardiopulmonary
Resuscitation, Athens, Greece.
Experimental-Research Center ELPEN Pharmaceutical, Athens, Greece.
Public Health Institute, Catholic University of Rome, Rome, Italy.
Department of Environmental, Biological
and Pharmaceutical Sciences and Technologies, Second University of Naples, Caserta, Italy.
Informatiche S.r.l., Vicenza, Italy. Correspondence and requests for materials should be addressed to E.L. (email:
Received: 24 March 2017
Accepted: 19 November 2017
Published: xx xx xxxx