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      Interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest

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          Abstract

          Purpose

          Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest.

          Methods

          Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague–Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N 2/98% O 2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N 2/98% O 2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H 2/98% O 2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel–Haenszel stratified analysis were used to explore the associations among gender, intervention and survival.

          Results

          The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel–Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention.

          Conclusion

          In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12872-021-02262-5.

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          Most cited references37

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          Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

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            Out-of-hospital cardiac arrest across the World: First report from the International Liaison Committee on Resuscitation (ILCOR)

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              Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications.

              Molecular hydrogen (H2) was believed to be inert and nonfunctional in mammalian cells. We overturned this concept by demonstrating that H2 reacts with highly reactive oxidants such as hydroxyl radical ((•)OH) and peroxynitrite (ONOO(-)) inside cells. H2 has several advantages exhibiting marked effects for medical applications: it is mild enough neither to disturb metabolic redox reactions nor to affect signaling by reactive oxygen species. Therefore, it should have no or little adverse effects. H2 can be monitored with an H2-specific electrode or by gas chromatography. H2 rapidly diffuses into tissues and cells to exhibit efficient effects. Thus, we proposed the potential of H2 for preventive and therapeutic applications. There are several methods to ingest or consume H2: inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline onto the eyes. Recent publications revealed that, in addition to the direct neutralization of highly reactive oxidants, H2 indirectly reduces oxidative stress by regulating the expression of various genes. Moreover, by regulating gene expression, H2 functions as an anti-inflammatory, antiallergic, and antiapoptotic molecule, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under way. Since most drugs specifically act on their specific targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has potential for clinical applications for many diseases.
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                Author and article information

                Contributors
                ycl0315@163.com
                lyq@tmmu.edu.cn
                Journal
                BMC Cardiovasc Disord
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central (London )
                1471-2261
                16 September 2021
                16 September 2021
                2021
                : 21
                : 441
                Affiliations
                [1 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Biomedical Engineering and Imaging Medicine, , Army Medical University, ; Chongqing, 400038 China
                [2 ]GRID grid.414287.c, ISNI 0000 0004 1757 967X, Department of Emergency, , Chongqing Emergency Medical Center, ; Chongqing, 400014 China
                [3 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Emergency, Southwest Hospital, , Army Medical University, ; Chongqing, 400038 China
                [4 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Intensive Care, Southwest Hospital, , Army Medical University, ; Chongqing, 400038 China
                Article
                2262
                10.1186/s12872-021-02262-5
                8443961
                33687157
                80320c43-d2e7-4a1e-8747-bd44158982fa
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 31 May 2021
                : 9 September 2021
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81701300
                Award ID: 31771070
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Cardiovascular Medicine
                cardiac arrest,cardiopulmonary resuscitation,hydrogen inhalation,neurological outcome,gender,target temperature management

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