Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management

Kei Hayashida, Motoaki Sano, Naomi Kamimura, Takashi Yokota, Masaru Suzuki, Shigeo Ohta, Keiichi Fukuda, Shingo Hori

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM).

Methods and Results-Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, postcardiac 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.

Original languageEnglish
Pages (from-to)2173-2180
Number of pages8
JournalCirculation
Volume130
Issue number24
DOIs
Publication statusPublished - 2014 Dec 9

Fingerprint

Heart Arrest
Resuscitation
Inhalation
Hydrogen
Temperature
Cardiopulmonary Resuscitation
Hyperoxia
Brain
Ventricular Fibrillation
Motor Activity
Therapeutics

Keywords

  • antioxidants
  • cardiopulmonary resuscitation
  • heart arrest
  • ischemia
  • reperfusion injury

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. / Hayashida, Kei; Sano, Motoaki; Kamimura, Naomi; Yokota, Takashi; Suzuki, Masaru; Ohta, Shigeo; Fukuda, Keiichi; Hori, Shingo.

In: Circulation, Vol. 130, No. 24, 09.12.2014, p. 2173-2180.

Research output: Contribution to journalArticle

Hayashida, Kei ; Sano, Motoaki ; Kamimura, Naomi ; Yokota, Takashi ; Suzuki, Masaru ; Ohta, Shigeo ; Fukuda, Keiichi ; Hori, Shingo. / Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. In: Circulation. 2014 ; Vol. 130, No. 24. pp. 2173-2180.
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AU - Hayashida, Kei

AU - Sano, Motoaki

AU - Kamimura, Naomi

AU - Yokota, Takashi

AU - Suzuki, Masaru

AU - Ohta, Shigeo

AU - Fukuda, Keiichi

AU - Hori, Shingo

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N2 - 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 2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM).Methods and Results-Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, postcardiac 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.

AB - 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 2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM).Methods and Results-Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, postcardiac 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.

KW - antioxidants

KW - cardiopulmonary resuscitation

KW - heart arrest

KW - ischemia

KW - reperfusion injury

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