Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics

Cardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rab...

Full description

Bibliographic Details
Main Authors: Yiyuan Zhang, Yang Feng, Fang Chen, Jiang Yu, Xiehong Liu, Yanjuan Liu, Jielin Ouyang, Mingyu Liang, Yiming Zhu, Lianhong Zou
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023034540
_version_ 1797818661998690304
author Yiyuan Zhang
Yang Feng
Fang Chen
Jiang Yu
Xiehong Liu
Yanjuan Liu
Jielin Ouyang
Mingyu Liang
Yiming Zhu
Lianhong Zou
author_facet Yiyuan Zhang
Yang Feng
Fang Chen
Jiang Yu
Xiehong Liu
Yanjuan Liu
Jielin Ouyang
Mingyu Liang
Yiming Zhu
Lianhong Zou
author_sort Yiyuan Zhang
collection DOAJ
description Cardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rabbits successfully resuscitated from 10-min asphyxia-induced CA were divided randomly into the normothermia (NT) group and mild therapeutic hypothermia (HT) group. The sham group underwent sham-operation. Survival was recorded and neurological deficit score (NDS) was assessed. The serum non-targeted metabolomics were detected using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) at 15 min, 3 h, 6 h and 24 h after return of spontaneous circulation (ROSC). Our study showed that the heart rate (HR) significantly slowed down during 0.5–6 h post ROSC, consistent with the decreasing trend of body temperature in the HT group. Compared with the NT group, the levels of Lac and PCO2 at 24 h post ROSC were lower, while a significant increase in PO2 level at 24 h post ROSC was observed in the HT group. The survival rate of the HT group was significantly higher than that of the NT group, and NDS scores were remarkably increased at 24 h post ROSC in the NT group. Significant differences in metabolic profiles at 15 min, 3 h, 6 h and 24 h post ROSC were observed among the Sham, NT and HT groups. The differential metabolites detected by UPLC-Q-TOF-MS/MS and GC-MS/MS were screened for further study between every two groups (NT vs sham, HT vs sham and HT vs NT) at 15 min, 3 h, 6 h and 24 h post ROSC. Phenylalanine metabolism, alanine, aspartate and glutamate metabolism and tricarboxylic acid (TCA) cycle were enriched in NT vs sham, HT vs sham and HT vs NT respectively. Our study demonstrated that therapeutic hypothermia improves the survival and neurological outcomes in rabbit model of cardiac arrest, and firstly represents the dynamic metabolic changes in the hypothermia therapy for CA by comprehensive UPLC-Q-TOF-MS/MS- and GC-MS/MS-based metabolomics.
first_indexed 2024-03-13T09:11:15Z
format Article
id doaj.art-b3f481175d6b4274afa6f1bc2ed6ed72
institution Directory Open Access Journal
issn 2405-8440
language English
last_indexed 2024-03-13T09:11:15Z
publishDate 2023-06-01
publisher Elsevier
record_format Article
series Heliyon
spelling doaj.art-b3f481175d6b4274afa6f1bc2ed6ed722023-05-27T04:26:04ZengElsevierHeliyon2405-84402023-06-0196e16247Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomicsYiyuan Zhang0Yang Feng1Fang Chen2Jiang Yu3Xiehong Liu4Yanjuan Liu5Jielin Ouyang6Mingyu Liang7Yiming Zhu8Lianhong Zou9The First Affiliated Hospital of Hunan Normal University, Hunan Provincial Key Laboratory of Molecular Epidemiology, Changsha, Hunan, ChinaThe First Affiliated Hospital of Hunan Normal University, Hunan Provincial Key Laboratory of Molecular Epidemiology, Changsha, Hunan, China; Department of Emergency Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, ChinaHunan Provincial People's Hospital, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics,Changsha, Hunan, ChinaHunan Provincial People's Hospital, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics,Changsha, Hunan, ChinaHunan Provincial People's Hospital, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics,Changsha, Hunan, ChinaHunan Provincial People's Hospital, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics,Changsha, Hunan, ChinaThe First Affiliated Hospital of Hunan Normal University, Hunan Provincial Key Laboratory of Molecular Epidemiology, Changsha, Hunan, China; Department of Emergency Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, ChinaThe First Affiliated Hospital of Hunan Normal University, Hunan Provincial Key Laboratory of Molecular Epidemiology, Changsha, Hunan, China; Department of Emergency Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, ChinaHunan Provincial People's Hospital, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics,Changsha, Hunan, China; Corresponding author. , Hunan Provincial Key Laboratory of Emergency and Critical Care Metabolomics, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, 61 Jiefang West Road, Changsha, Hunan 410005, PR China.The First Affiliated Hospital of Hunan Normal University, Hunan Provincial Key Laboratory of Molecular Epidemiology, Changsha, Hunan, China; Corresponding author. Department of Emergency Medicine, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, 61 Jiefang West Road, Changsha, Hunan 410005, PR China.Cardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rabbits successfully resuscitated from 10-min asphyxia-induced CA were divided randomly into the normothermia (NT) group and mild therapeutic hypothermia (HT) group. The sham group underwent sham-operation. Survival was recorded and neurological deficit score (NDS) was assessed. The serum non-targeted metabolomics were detected using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) at 15 min, 3 h, 6 h and 24 h after return of spontaneous circulation (ROSC). Our study showed that the heart rate (HR) significantly slowed down during 0.5–6 h post ROSC, consistent with the decreasing trend of body temperature in the HT group. Compared with the NT group, the levels of Lac and PCO2 at 24 h post ROSC were lower, while a significant increase in PO2 level at 24 h post ROSC was observed in the HT group. The survival rate of the HT group was significantly higher than that of the NT group, and NDS scores were remarkably increased at 24 h post ROSC in the NT group. Significant differences in metabolic profiles at 15 min, 3 h, 6 h and 24 h post ROSC were observed among the Sham, NT and HT groups. The differential metabolites detected by UPLC-Q-TOF-MS/MS and GC-MS/MS were screened for further study between every two groups (NT vs sham, HT vs sham and HT vs NT) at 15 min, 3 h, 6 h and 24 h post ROSC. Phenylalanine metabolism, alanine, aspartate and glutamate metabolism and tricarboxylic acid (TCA) cycle were enriched in NT vs sham, HT vs sham and HT vs NT respectively. Our study demonstrated that therapeutic hypothermia improves the survival and neurological outcomes in rabbit model of cardiac arrest, and firstly represents the dynamic metabolic changes in the hypothermia therapy for CA by comprehensive UPLC-Q-TOF-MS/MS- and GC-MS/MS-based metabolomics.http://www.sciencedirect.com/science/article/pii/S2405844023034540Cardiac arrestMetabolomicsUPLC-Q-TOF-MS/MSGC-MS/MSHypothermia
spellingShingle Yiyuan Zhang
Yang Feng
Fang Chen
Jiang Yu
Xiehong Liu
Yanjuan Liu
Jielin Ouyang
Mingyu Liang
Yiming Zhu
Lianhong Zou
Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
Heliyon
Cardiac arrest
Metabolomics
UPLC-Q-TOF-MS/MS
GC-MS/MS
Hypothermia
title Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
title_full Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
title_fullStr Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
title_full_unstemmed Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
title_short Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics
title_sort insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of gc ms ms and uplc q tof ms ms based on serum metabolomics
topic Cardiac arrest
Metabolomics
UPLC-Q-TOF-MS/MS
GC-MS/MS
Hypothermia
url http://www.sciencedirect.com/science/article/pii/S2405844023034540
work_keys_str_mv AT yiyuanzhang insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT yangfeng insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT fangchen insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT jiangyu insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT xiehongliu insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT yanjuanliu insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT jielinouyang insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT mingyuliang insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT yimingzhu insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics
AT lianhongzou insightintothemechanismsoftherapeutichypothermiaforasphyxiacardiacarrestusingacomprehensiveapproachofgcmsmsanduplcqtofmsmsbasedonserummetabolomics