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Hydrogen-Rich Saline Improves Survival and Neurological Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation in Rats

Huo, Ting-ting MD, PhD*; Zeng, Yi MD, PhD*; Liu, Xiao-nan MD, PhD; Sun, Li MD, PhD; Han, Huan-zhi MD§; Chen, Hong-guang MD§; Lu, Zhi-hong MD, PhD*; Huang, Yi MD, PhD*; Nie, Huang MD, PhD*; Dong, Hai-long MD, PhD*; Xie, Ke-liang MD, PhD§; Xiong, Li-ze MD, PhD*

doi: 10.1213/ANE.0000000000000303
Critical Care, Trauma, and Resuscitation: Research Report

BACKGROUND: Sudden cardiac arrest is a leading cause of death worldwide. Three-fourths of cardiac arrest patients die before hospital discharge or experience significant neurological damage. Hydrogen-rich saline, a portable, easily administered, and safe means of delivering hydrogen gas, can exert organ-protective effects through regulating oxidative stress, inflammation, and apoptosis. We designed this study to investigate whether hydrogen-rich saline treatment could improve survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation, and the mechanism responsible for this effect.

METHODS: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by asphyxia. Different doses of hydrogen-rich saline or normal saline were administered IV at 1 minute before cardiopulmonary resuscitation, followed by injections at 6 and 12 hours after restoration of spontaneous circulation, respectively. We assessed survival, neurological outcome, oxidative stress, inflammation biomarkers, and apoptosis.

RESULTS: Hydrogen-rich saline treatment dose dependently improved survival and neurological function after cardiac arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently ameliorated brain injury after cardiac arrest/resuscitation, which was characterized by the increase of survival neurons in hippocampus CA1, reduction of brain edema in cortex and hippocampus, preservation of blood-brain barrier integrity, as well as the decrease of serum S100β and neuron-specific enolase. Furthermore, we found that the beneficial effects of hydrogen-rich saline treatment were associated with decreased levels of oxidative products (8-iso-prostaglandin F2α and malondialdehyde) and inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and high-mobility group box protein 1), as well as the increased activity of antioxidant enzymes (superoxide dismutase and catalase) in serum and brain tissues. In addition, hydrogen-rich saline treatment reduced caspase-3 activity in cortex and hippocampus after cardiac arrest/resuscitation.

CONCLUSIONS: Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.

Published ahead of print June 17, 2014.

From the Departments of *Anesthesiology, and Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province; Department of Anesthesia and Operation Center, Chinese People’s Liberation Army General Hospital & Medical School of Chinese People’s Liberation Army, Beijing; and §Department of Anesthesiology, Tianjin Institute of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, P. R. China.

Accepted for publication February 26, 2014.

Published ahead of print June 17, 2014.

Funding: This work was supported by research grants from the National Natural Science Foundation of China (30930091 to Li-ze Xiong, 81101409 to Ke-liang Xie, 30600840 to Zhi-hong Lu, 81271195 to Yi Zeng), the Natural Science Foundation of Tianjin (13JCQNJC11400 to Ke-liang Xie), and the Foundation of Tianjin Bureau of Public Health (2011KZ108 to Ke-liang Xie).

The authors declare no conflicts of interest.

Drs. Ting-ting Huo, Yi Zeng, and Xiao-nan Liu contributed equally to this work.

Reprints will not be available from the authors.

Address correspondence to Li-ze Xiong, MD, PhD, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, P. R. China. Address e-mail to

© 2014 International Anesthesia Research Society