title: Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management.
abstract: BACKGROUND
  We have previously shown that hydrogen (H2) inhalation, begun at the start of hyperoxic cardiopulmonary resuscitation, significantly improves brain and cardiac function in a rat model of cardiac arrest. Here, we examine the effectiveness of this therapeutic approach when H2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM).
  
  
  RESULTS
  Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, post-cardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O2 and normothermia (control); mechanically ventilated with 26% O2, 1.3% H2, and normothermia (H2); mechanically ventilated with 26% O2 and TTM (TTM); and mechanically ventilated with 26% O2, 1.3% H2, and TTM (TTM+H2). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in the H2 and TTM groups, and 85.7% in the TTM+H2 group. Combined therapy of TTM and H2 inhalation was superior to TTM alone in terms of neurological deficit scores at 24, 48, and 72 hours after ROSC, and motor activity at 7 days after ROSC. Neuronal degeneration and microglial activation in a vulnerable brain region was suppressed by both TTM alone and H2 inhalation alone, with the combined therapy of TTM and H2 inhalation being most effective.
  
  
  CONCLUSIONS
  H2 inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H2 inhalation was more effective than TTM alone.
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Kei
authors.initials: K
authors.lastname: Hayashida
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.). msano@a8.keio.jp.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Masaru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: From the Department of Emergency and Critical Care Medicine (K.H., M.S., S.H.) and Department of Cardiology (M.S., K.F.), School of Medicine, Keio University, Tokyo, Japan; and Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kanagawa, Japan (N.K., T.Y., S.O.).
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001775:Blood Circulation / Q000502:physiology; D001831:Body Temperature / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D006323:Heart Arrest / Q000150:complications* / Q000209:etiology; D006624:Hippocampus / Q000502:physiology; D006859:Hydrogen / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D014693:Ventricular Fibrillation / Q000150:complications
chemical_list: D006859:Hydrogen
keywords: antioxidants; cardiopulmonary resuscitation; heart arrest; ischemia; reperfusion injury