title: Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Huan-Zhi
authors.initials: HZ
authors.lastname: Han
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Chen
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Huang
authors.initials: H
authors.lastname: Nie
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Dong
authors.forename: Ke-Liang
authors.initials: KL
authors.lastname: Xie
authors.forename: Li-Ze
authors.initials: LZ
authors.lastname: Xiong
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005440:Fluid Therapy / Q000379:methods*; D006323:Heart Arrest / Q000175:diagnosis / Q000628:therapy*; D006859:Hydrogen / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012965:Sodium Chloride / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; C075750:8-epi-prostaglandin F2alpha; D012965:Sodium Chloride; D008315:Malondialdehyde; D006859:Hydrogen; D015237:Dinoprost; C505410:Casp3 protein, rat; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase