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代谢组学分析揭示了窒息性和心律失常性心脏骤停动物模型中的不同模式。

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

机构信息

Medical School, National and Kapodistrian University of Athens, Athens, Greece.

European University Cyprus, Nicosia, Cyprus.

出版信息

Sci Rep. 2017 Nov 29;7(1):16575. doi: 10.1038/s41598-017-16857-6.

DOI:10.1038/s41598-017-16857-6
PMID:29185486
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5707403/
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 H 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.

摘要

心脏骤停(CA)不是一种均匀的状态,其病理生理学强烈依赖于其原因。在这项工作中,我们使用代谢组学方法来研究猪模型血浆样本在两种不同的 CA 原因(窒息(ACA)和心室颤动(VFCA))后发生的动态代谢变化。在实验阶段,在基线和每分钟收集血浆样本。为了确定表征两种病理实体的代谢组学特征,所有样本均通过 H NMR 光谱和 LC-MS/MS 光谱进行分析。ACA 和 VFCA 的代谢组学特征在心脏骤停前和复苏阶段明显不同。在与三羧酸(TCA)循环、尿素循环和 TCA 的补充有关的代谢物的血浆浓度中观察到主要的改变。ACA 动物在窒息和 CA 期间表现出明显的代谢紊乱,而对于 VFCA 动物,这种现象在复苏阶段发生了转移。有趣的是,从窒息阶段开始,根据其代谢组学特征,ACA 动物被分为两组,这与临床结果相关。在预后较差的动物中观察到琥珀酸的过度产生,表明该代谢物可能具有潜在的预后作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/a2a58955fbc7/41598_2017_16857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/ef56c557001e/41598_2017_16857_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/3ffbdf9500dc/41598_2017_16857_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/1b516f07c724/41598_2017_16857_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/f9edebb2d1bb/41598_2017_16857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/a2a58955fbc7/41598_2017_16857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/ef56c557001e/41598_2017_16857_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/3ffbdf9500dc/41598_2017_16857_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/1b516f07c724/41598_2017_16857_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/f9edebb2d1bb/41598_2017_16857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8835/5707403/a2a58955fbc7/41598_2017_16857_Fig5_HTML.jpg

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