Inhalation of hydrogen gases in acute cerebral infarctionScientific Research

Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection

DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.012

Abstract

Background

Molecular hydrogen (H2) acts as a therapeutic antioxidant. In several animal studies, inhalation of H2 gas (1-4%) was effective in improving cerebral infarction. Therefore, for practical application, randomized controlled clinical trials are needed to evaluate the effect of H2 gas inhalation. Here, we evaluate H2 for the treatment of acute cerebral infarction.

Methods

Through this randomized controlled clinical trial, we evaluated the safety and efficacy of H2 therapy in patients with acute-phase cerebral infarction with mild to moderate National Institutes of Health Stroke Scale (NIHSS) score (NIHSS =2-6) . We recruited 50 patients (25 each in the H2 and control groups) with a treatment window of 6 to 24 hours. The H2 group received 3% H2 gas inhalation (twice a day, 1 hour each time), and the control group received conventional intravenous drug therapy for the first 7 days.The evaluations included daily vital signs, NIHSS scores, physical therapy indices, weekly blood chemistry, and brain magnetic resonance imaging (MRI) scans over the 2-week study period.

Results

The H2 group showed no significant adverse effects with improvements in oxygen saturation. The following significant effects were found: the relative signal intensity of MRI, which indicated the severity of the infarction site, NIHSS scores for clinically quantifying stroke severity, and physical therapy evaluation, as judged by the Barthel Index.

Conclusions

H2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H2 gas.

References

    • Ohsawa I.
    • Ishikawa M.
    • Takahashi K.
    • et al.
    Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.

    Nat Med. 2007; 13: 688-694

    View in Article

    • Hayashida K.
    • Sano M.
    • Kamimura N.
    • et al.
    Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management.

    Circulation. 2014; 130: 2173-2180

    View in Article

    • Ohta S.
    Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.

    Pharmacol Ther. 2014; 144: 1-11

    View in Article

    • Ichihara M.
    • Sobue S.
    • Ito M.
    • et al.
    Beneficial biological effects and the underlying mechanisms of molecular hydrogen—comprehensive review of 321 original articles.

    Med Gas Res. 2015; 5: 12

    View in Article

    • Ono H.
    • Nishijima Y.
    • Adachi N.
    • et al.
    A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level.

    Med Gas Res. 2012; 2: 21

    View in Article

    • Tamura T.
    • Hayashida K.
    • Sano M.
    • et al.
    Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome—first-in-human pilot study.

    Circ J. 2016; 80: 1870-1873

    View in Article

    • Adams Jr, H.P.
    • Bendixen B.H.
    • Kappelle L.J.
    • et al.
    Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST.

    Stroke. 1993; 24: 35-41

    View in Article

    • Seki H.
    • Kuromaki K.
    • Takeda S.
    • et al.
    The possibility of clinical application of the thromboxane A2 synthase inhibitor, ozagrel, for the treatment and prevention of preeclampsia: a preliminary report.

    J Obstet Gynaecol (Tokyo 1995). 1995; 21: 357-365

    View in Article

    • Sharma P.
    • Sinha M.
    • Shukla R.
    • et al.
    A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke.

    Ann Indian Acad Neurol. 2011; 14: 103-106

    View in Article

    • Asadi H.
    • Yan B.
    • Dowling R.
    • et al.
    Advances in medical revascularisation treatments in acute ischemic stroke.

    Thrombosis. 2014; 2014: 714218

    View in Article

    • Quinn T.J.
    • Langhorne P.
    • Stott D.J.
    Barthel Index for stroke trials: development, properties, and application.

    Stroke. 2011; 42: 1146-1151

    View in Article

    • Safaz I.
    • Yilmaz B.
    • Yasar E.
    • et al.
    Brunnstrom recovery stage and Motricity Index for the evaluation of upper extremity in stroke: analysis for correlation and responsiveness.

    Int J Rehabil Res. 2009; 32: 228-231

    View in Article

    • Banks J.L.
    • Marotta C.A.
    Outcomes validity and reliability of the modified Rankin Scale: implications for stroke clinical trials: a literature review and synthesis.

    Stroke. 2007; 38: 1091-1096

    View in Article

    • Stineman M.G.
    • Jette A.
    • Fiedler R.
    • et al.
    Impairment-specific dimensions within the Functional Independence Measure.

    Arch Phys Med Rehabil. 1997; 78: 636-643

    View in Article

    • Lansberg M.G.
    • Thijs V.N.
    • O’Brien M.W.
    • et al.
    Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke.

    AJNR Am J Neuroradiol. 2001; 22: 637-644

    View in Article

    • Albach F.N.
    • Brunecker P.
    • Usnich T.
    • et al.
    Complete early reversal of diffusion-weighted imaging hyperintensities after ischemic stroke is mainly limited to small embolic lesions.

    Stroke. 2013; 44: 1043-1048

    View in Article

    • Lee J.M.
    • Grabb M.C.
    • Zipfel G.J.
    • et al.
    Brain tissue responses to ischemia.

    J Clin Invest. 2000; 106: 723-731

    View in Article

    • Iuchi K.
    • Imoto A.
    • Kamimura N.
    • et al.
    Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators.

    Sci Rep. 2016; 6: 18971

    View in Article

    • Ren Y.
    • Wei B.
    • Song X.
    • et al.
    Edaravone’s free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature.

    Int J Neurosci. 2015; 125: 555-565

    View in Article

    • Moriguchi A.
    • Aoki T.
    • Mihara K.
    • et al.
    Antithrombotic effects of FK419, a novel nonpeptide platelet GPIIb/IIIa antagonist, in a guinea pig photochemically induced middle cerebral artery thrombosis model: comparison with ozagrel and argatroban.

    J Pharmacol Exp Ther. 2004; 308: 1094-1101

    View in Article

DOI: 10.1016

Published on: 29/06/2017

Authors:

Ono H, Nishijima Y, Ohta S, et al.

Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection

DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.012

Abstract

Background

Molecular hydrogen (H2) acts as a therapeutic antioxidant. In several animal studies, inhalation of H2 gas (1-4%) was effective in improving cerebral infarction. Therefore, for practical application, randomized controlled clinical trials are needed to evaluate the effect of H2 gas inhalation. Here, we evaluate H2 for the treatment of acute cerebral infarction.

Methods

Through this randomized controlled clinical trial, we evaluated the safety and efficacy of H2 therapy in patients with acute-phase cerebral infarction with mild to moderate National Institutes of Health Stroke Scale (NIHSS) score (NIHSS =2-6) . We recruited 50 patients (25 each in the H2 and control groups) with a treatment window of 6 to 24 hours. The H2 group received 3% H2 gas inhalation (twice a day, 1 hour each time), and the control group received conventional intravenous drug therapy for the first 7 days.The evaluations included daily vital signs, NIHSS scores, physical therapy indices, weekly blood chemistry, and brain magnetic resonance imaging (MRI) scans over the 2-week study period.

Results

The H2 group showed no significant adverse effects with improvements in oxygen saturation. The following significant effects were found: the relative signal intensity of MRI, which indicated the severity of the infarction site, NIHSS scores for clinically quantifying stroke severity, and physical therapy evaluation, as judged by the Barthel Index.

Conclusions

H2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H2 gas.

References

    • Ohsawa I.
    • Ishikawa M.
    • Takahashi K.
    • et al.
    Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.

    Nat Med. 2007; 13: 688-694

    View in Article

    • Hayashida K.
    • Sano M.
    • Kamimura N.
    • et al.
    Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management.

    Circulation. 2014; 130: 2173-2180

    View in Article

    • Ohta S.
    Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.

    Pharmacol Ther. 2014; 144: 1-11

    View in Article

    • Ichihara M.
    • Sobue S.
    • Ito M.
    • et al.
    Beneficial biological effects and the underlying mechanisms of molecular hydrogen—comprehensive review of 321 original articles.

    Med Gas Res. 2015; 5: 12

    View in Article

    • Ono H.
    • Nishijima Y.
    • Adachi N.
    • et al.
    A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level.

    Med Gas Res. 2012; 2: 21

    View in Article

    • Tamura T.
    • Hayashida K.
    • Sano M.
    • et al.
    Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome—first-in-human pilot study.

    Circ J. 2016; 80: 1870-1873

    View in Article

    • Adams Jr, H.P.
    • Bendixen B.H.
    • Kappelle L.J.
    • et al.
    Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST.

    Stroke. 1993; 24: 35-41

    View in Article

    • Seki H.
    • Kuromaki K.
    • Takeda S.
    • et al.
    The possibility of clinical application of the thromboxane A2 synthase inhibitor, ozagrel, for the treatment and prevention of preeclampsia: a preliminary report.

    J Obstet Gynaecol (Tokyo 1995). 1995; 21: 357-365

    View in Article

    • Sharma P.
    • Sinha M.
    • Shukla R.
    • et al.
    A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke.

    Ann Indian Acad Neurol. 2011; 14: 103-106

    View in Article

    • Asadi H.
    • Yan B.
    • Dowling R.
    • et al.
    Advances in medical revascularisation treatments in acute ischemic stroke.

    Thrombosis. 2014; 2014: 714218

    View in Article

    • Quinn T.J.
    • Langhorne P.
    • Stott D.J.
    Barthel Index for stroke trials: development, properties, and application.

    Stroke. 2011; 42: 1146-1151

    View in Article

    • Safaz I.
    • Yilmaz B.
    • Yasar E.
    • et al.
    Brunnstrom recovery stage and Motricity Index for the evaluation of upper extremity in stroke: analysis for correlation and responsiveness.

    Int J Rehabil Res. 2009; 32: 228-231

    View in Article

    • Banks J.L.
    • Marotta C.A.
    Outcomes validity and reliability of the modified Rankin Scale: implications for stroke clinical trials: a literature review and synthesis.

    Stroke. 2007; 38: 1091-1096

    View in Article

    • Stineman M.G.
    • Jette A.
    • Fiedler R.
    • et al.
    Impairment-specific dimensions within the Functional Independence Measure.

    Arch Phys Med Rehabil. 1997; 78: 636-643

    View in Article

    • Lansberg M.G.
    • Thijs V.N.
    • O’Brien M.W.
    • et al.
    Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke.

    AJNR Am J Neuroradiol. 2001; 22: 637-644

    View in Article

    • Albach F.N.
    • Brunecker P.
    • Usnich T.
    • et al.
    Complete early reversal of diffusion-weighted imaging hyperintensities after ischemic stroke is mainly limited to small embolic lesions.

    Stroke. 2013; 44: 1043-1048

    View in Article

    • Lee J.M.
    • Grabb M.C.
    • Zipfel G.J.
    • et al.
    Brain tissue responses to ischemia.

    J Clin Invest. 2000; 106: 723-731

    View in Article

    • Iuchi K.
    • Imoto A.
    • Kamimura N.
    • et al.
    Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators.

    Sci Rep. 2016; 6: 18971

    View in Article

    • Ren Y.
    • Wei B.
    • Song X.
    • et al.
    Edaravone’s free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature.

    Int J Neurosci. 2015; 125: 555-565

    View in Article

    • Moriguchi A.
    • Aoki T.
    • Mihara K.
    • et al.
    Antithrombotic effects of FK419, a novel nonpeptide platelet GPIIb/IIIa antagonist, in a guinea pig photochemically induced middle cerebral artery thrombosis model: comparison with ozagrel and argatroban.

    J Pharmacol Exp Ther. 2004; 308: 1094-1101

    View in Article

References
HBS10 - Home Hydrogen Therapy Equipment

HBS10

Home Hydrogen Therapy Equipment

Explore HBS10