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Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

摘要Background:Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA).However,brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology.Methods:To clarify the metabolomics profiling of ASCP,12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group,n =6) and without (DHCA [D] group,n =6) ASCP according to the random number table.ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery.Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass.The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry.Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites,and then Student's t-test was applied to test for statistical significance between the two groups.Results:Metabolic profiling of brain was distinctive significantly between the two groups (Q2y =0.88 for partial least squares-DA model).In comparing to group D,62 definable metabolites were varied significantly after ASCP,which were mainly related to amino acid metabolism,carbohydrate metabolism,and lipid metabolism.Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway,subdued anaerobic metabolism,and oxidative stress.In addition,L-kynurenine (P =0.0019),5-methoxyindole-3-acetic acid (P =0.0499),and 5-hydroxyindole-3-acetic acid (P =0.0495) in tryptophan metabolism pathways were decreased,and citrulline (P =0.0158) in urea cycle was increased in group DA comparing to group D.Conclusions:The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP,and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.

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作者单位 Department of Cardiopulmonary Bypass, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China [1] Department of Surgery and Center for Pediatric Cardiac Surgery, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China [2]
栏目名称 Original Articles
DOI 10.4103/0366-6999.178012
发布时间 2016-04-18
基金项目
the grants from National Natural Science Foundation of China
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中华医学杂志(英文版)

中华医学杂志(英文版)

2016年129卷6期

702-708页

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