Hydrogen therapy after resuscitation improves myocardial injury involving inhibition of autophagy in an asphyxial rat model of cardiac arrest

Gong,Xiaohui; Fan,Xinhui; Yin,Xinxin; Xu,Tonghui; Li,Jiaxin; Guo,Jialin; Zhao,Xiangkai; Wei,Shujian; Yuan,Qiuhuan; Wang,Jiali; Han,Xuchen; Chen,Yuguo

doi:10.3892/etm.2022.11302

Hydrogen therapy after resuscitation improves myocardial injury involving inhibition of autophagy in an asphyxial rat model of cardiac arrest

Authors:
- Xiaohui Gong
- Xinhui Fan
- Xinxin Yin
- Tonghui Xu
- Jiaxin Li
- Jialin Guo
- Xiangkai Zhao
- Shujian Wei
- Qiuhuan Yuan
- Jiali Wang
- Xuchen Han
- Yuguo Chen
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Affiliations: Department of Emergency Medicine, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Emergency Medicine, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia Autonomous Region 024005, P.R. China
Published online on: April 7, 2022 https://doi.org/10.3892/etm.2022.11302
Article Number: 376
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hydrogen (H₂) therapy is a therapeutic strategy using molecular H₂. Due to its ability to regulate cell homeostasis, H₂ therapy has exhibited marked therapeutic effects on a number of oxidative stress‑associated diseases. The present study investigated the effectiveness of H₂ therapy in protecting against myocardial injury in a rat model of asphyxial cardiac arrest and cardiopulmonary resuscitation. Rats underwent 10‑min asphyxia‑induced cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and were randomly divided into control and H₂ therapy groups. After resuscitation, the H₂ therapy group was administered room air mixed with 2% H₂ gas for respiration. During CA/CPR, the arterial pressure and heart rate were measured every minute. Survival rate, cardiac function, myocardial injury biomarkers creatine kinase‑MB and cardiac troponin‑T, and histopathological changes were evaluated to determine the protective effects of H₂ therapy in CA/CPR. Immunohistochemistry and western blot analysis were used to determine the expression levels of autophagy‑associated proteins. In vitro, H9C2 cells were subjected to hypoxia/reoxygenation and H₂‑rich medium was used in H₂ treatment groups. Western blotting and immunofluorescence were used to observe the expression levels of autophagy‑associated proteins. Moreover, an adenovirus‑monomeric red fluorescent protein‑green fluorescent protein‑LC3 construct was used to explore the dynamics of autophagy in the H9C2 cells. The results showed that H₂ therapy significantly improved post‑resuscitation survival and cardiac function. H₂ therapy also improved mitochondrial mass and decreased autophagosome numbers in cardiomyocytes after resuscitation. The treatment inhibited autophagy activation, with lower expression levels of autophagy‑associated proteins and decreased autophagosome formation in vivo and vitro. In conclusion, H₂ gas inhalation after return of spontaneous circulation improved cardiac function via the inhibition of autophagy.

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