Hydrogen therapy through a nasal cannula with a small flow of the gasScientific Research

Hydrogen therapy through a nasal cannula with a small flow of the gas

J Clin Med Res and Elmer Press Inc

doi: https://doi.org/10.14740/jocmr4323

Abstract

Molecular hydrogen (H 2 ) is a biologically active gas that is widely used in the healthcare sector. In recent years, hydrogen generators that produce the gas at the point of consumption, in hospitals, clinics, medical centers, salons, etc., have become popular in healthcare. Often, these generators produce H 2 at a low flow rate, as a result of which their efficiency is low. This study aims to evaluate the concentration in the body of H 2 delivered by hydrogen gas generators through a nasal cannula.

Methods

We administered 100% H 2 produced by an H 2 gas generator at a low flow rate of 250 ml/min via a nasal cannula to three piglets. An oxygen mask is placed over the nasal cannula to limit hydrogen leakage, and a catheter is placed in the carotid artery to monitor arterial hydrogen concentration.

Results

During the first hour of hydrogen inhalation, the mean (standard error (SE)) H 2 concentrations and saturation in the arterial blood of the three pigs was 1560 (413) Nl/ml and 8.85% (2.34%); 1.190 (102) nL/ml and 6.74% (0.58%); and 1.740 (181) nL/mL and 9.88% (1.03%), respectively.

Conclusions

Inhalation of 100% hydrogen produced by a hydrogen generator, even at low flow rates, can increase blood hydrogen concentration to levels that previous nonclinical and clinical studies have shown to be therapeutically effective. The combination of a nasal cannula and an oxygen mask is a convenient way to reduce H 2 leakage while maintaining oxygen content.

References

Mizuno K, Sasaki AT, Ebisu K, Tajima K, Kajimoto O, Nojima J, Kuratsune H, et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2017;7(4):247-255.
doi pubmed
Yoon YS, Sajo ME, Ignacio RM, Kim SK, Kim CS, Lee KJ. Positive Effects of hydrogen water on 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Biol Pharm Bull. 2014;37(9):1480-1485.
doi pubmed
Fang S, Li X, Wei X, Zhang Y, Ma Z, Wei Y, Wang W. Beneficial effects of hydrogen gas inhalation on a murine model of allergic rhinitis. Exp Ther Med. 2018;16(6):5178-5184.
doi pubmed
Ishibashi T, Sato B, Rikitake M, Seo T, Kurokawa R, Hara Y, Naritomi Y, et al. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res. 2012;2(1):27.
doi pubmed
Zhang N, Deng C, Zhang X, Zhang J, Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma Res Pract. 2018;4:3.
doi pubmed
Lu W, Li D, Hu J, Mei H, Shu J, Long Z, Yuan L, et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J Thorac Dis. 2018;10(6):3232-3243.
doi pubmed
Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X, Shi JD, et al. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J Thorac Dis. 2020;12(6):3448-3452.
doi pubmed
Zhang Y, Su WJ, Chen Y, Wu TY, Gong H, Shen XL, Wang YX, et al. Effects of hydrogen-rich water on depressive-like behavior in mice. Sci Rep. 2016;6:23742.
doi pubmed
Li J, Wang C, Zhang JH, Cai JM, Cao YP, Sun XJ. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res. 2010;1328:152-161.
doi pubmed
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688-694.
doi pubmed
Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Maekawa Y, Kawamura A, et al. H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. J Am Heart Assoc. 2012;1(5):e003459.
doi pubmed
Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Ohta S, Fukuda K, 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(24):2173-2180.
doi pubmed
Kumagai K, Toyooka T, Takeuchi S, Otani N, Wada K, Tomiyama A, Mori K. Hydrogen gas inhalation improves delayed brain injury by alleviating early brain injury after experimental subarachnoid hemorrhage. Sci Rep. 2020;10(1):12319.
doi pubmed
Satoh Y, Araki Y, Kashitani M, Nishii K, Kobayashi Y, Fujita M, Suzuki S, et al. Molecular hydrogen prevents social deficits and depression-like behaviors induced by low-intensity blast in mice. J Neuropathol Exp Neurol. 2018;77(9):827-836.
doi pubmed
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30-35.
doi pubmed
Yoshida A, Asanuma H, Sasaki H, Sanada S, Yamazaki S, Asano Y, Shinozaki Y, et al. H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther. 2012;26(3):217-226.
doi pubmed
Katsumata Y, Sano F, Abe T, Tamura T, Fujisawa T, Shiraishi Y, Kohsaka S, et al. The Effects of hydrogen gas inhalation on adverse left ventricular remodeling after percutaneous coronary intervention for ST-elevated myocardial infarction- first pilot study in humans. Circ J. 2017;81(7):940-947.
doi pubmed
Chen J, Zhang H, Hu J, Gu Y, Shen Z, Xu L, Jia X, et al. Hydrogen-rich saline alleviates kidney fibrosis following AKI and retains klotho expression. Front Pharmacol. 2017;8:499.
doi pubmed
Qiu P, Liu Y, Zhang J. Recent advances in studies of molecular hydrogen against sepsis. Int J Biol Sci. 2019;15(6):1261-1275.
doi pubmed
Matsuoka T, Suzuki M, Sano M, Hayashida K, Tamura T, Homma K, Fukuda K, et al. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017;83(3):469-475.
doi pubmed
Tamura T, Sano M, Matsuoka T, Yoshizawa J, Yamamoto R, Katsumata Y, Endo J, et al. Hydrogen gas inhalation attenuates endothelial glycocalyx damage and stabilizes hemodynamics in a rat hemorrhagic shock model. Shock. 2020;54(3):377-385.
doi pubmed
Li S, Liao R, Sheng X, Luo X, Zhang X, Wen X, Zhou J, et al. Hydrogen gas in cancer treatment. Front Oncol. 2019;9:696.
doi pubmed
Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, Ohta S. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016;6:18971.
doi pubmed
Tamura T, Suzuki M, Hayashida K, Kobayashi Y, Yoshizawa J, Shibusawa T, Sano M, et al. Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome. J Clin Biochem Nutr. 2020; Epub ahead of print.
doi pubmed
Kobayashi E, Sano M. Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs. PLoS One. 2019;14(10):e0222863.
doi pubmed
Sano M, Ichihara G, Katsumata Y, Hiraide T, Hirai A, Momoi M, Tamura T, et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One. 2020;15(6):e0234626.
doi pubmed
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.
doi pubmed


DOI: 10.14740

Published on: 20201208


Authors:

Motoaki Sano а, б, г , Kohsuke Ширакава а, Ь , Yoshinori Кацумата а, Ь , Genki Ichihara а, Ь , Eiji Kobayashi

Hydrogen therapy through a nasal cannula with a small flow of the gas

J Clin Med Res and Elmer Press Inc

doi: https://doi.org/10.14740/jocmr4323

Abstract

Molecular hydrogen (H 2 ) is a biologically active gas that is widely used in the healthcare sector. In recent years, hydrogen generators that produce the gas at the point of consumption, in hospitals, clinics, medical centers, salons, etc., have become popular in healthcare. Often, these generators produce H 2 at a low flow rate, as a result of which their efficiency is low. This study aims to evaluate the concentration in the body of H 2 delivered by hydrogen gas generators through a nasal cannula.

Methods

We administered 100% H 2 produced by an H 2 gas generator at a low flow rate of 250 ml/min via a nasal cannula to three piglets. An oxygen mask is placed over the nasal cannula to limit hydrogen leakage, and a catheter is placed in the carotid artery to monitor arterial hydrogen concentration.

Results

During the first hour of hydrogen inhalation, the mean (standard error (SE)) H 2 concentrations and saturation in the arterial blood of the three pigs was 1560 (413) Nl/ml and 8.85% (2.34%); 1.190 (102) nL/ml and 6.74% (0.58%); and 1.740 (181) nL/mL and 9.88% (1.03%), respectively.

Conclusions

Inhalation of 100% hydrogen produced by a hydrogen generator, even at low flow rates, can increase blood hydrogen concentration to levels that previous nonclinical and clinical studies have shown to be therapeutically effective. The combination of a nasal cannula and an oxygen mask is a convenient way to reduce H 2 leakage while maintaining oxygen content.

References

Mizuno K, Sasaki AT, Ebisu K, Tajima K, Kajimoto O, Nojima J, Kuratsune H, et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2017;7(4):247-255.
doi pubmed
Yoon YS, Sajo ME, Ignacio RM, Kim SK, Kim CS, Lee KJ. Positive Effects of hydrogen water on 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Biol Pharm Bull. 2014;37(9):1480-1485.
doi pubmed
Fang S, Li X, Wei X, Zhang Y, Ma Z, Wei Y, Wang W. Beneficial effects of hydrogen gas inhalation on a murine model of allergic rhinitis. Exp Ther Med. 2018;16(6):5178-5184.
doi pubmed
Ishibashi T, Sato B, Rikitake M, Seo T, Kurokawa R, Hara Y, Naritomi Y, et al. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res. 2012;2(1):27.
doi pubmed
Zhang N, Deng C, Zhang X, Zhang J, Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma Res Pract. 2018;4:3.
doi pubmed
Lu W, Li D, Hu J, Mei H, Shu J, Long Z, Yuan L, et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J Thorac Dis. 2018;10(6):3232-3243.
doi pubmed
Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X, Shi JD, et al. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J Thorac Dis. 2020;12(6):3448-3452.
doi pubmed
Zhang Y, Su WJ, Chen Y, Wu TY, Gong H, Shen XL, Wang YX, et al. Effects of hydrogen-rich water on depressive-like behavior in mice. Sci Rep. 2016;6:23742.
doi pubmed
Li J, Wang C, Zhang JH, Cai JM, Cao YP, Sun XJ. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res. 2010;1328:152-161.
doi pubmed
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688-694.
doi pubmed
Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Maekawa Y, Kawamura A, et al. H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. J Am Heart Assoc. 2012;1(5):e003459.
doi pubmed
Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Ohta S, Fukuda K, 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(24):2173-2180.
doi pubmed
Kumagai K, Toyooka T, Takeuchi S, Otani N, Wada K, Tomiyama A, Mori K. Hydrogen gas inhalation improves delayed brain injury by alleviating early brain injury after experimental subarachnoid hemorrhage. Sci Rep. 2020;10(1):12319.
doi pubmed
Satoh Y, Araki Y, Kashitani M, Nishii K, Kobayashi Y, Fujita M, Suzuki S, et al. Molecular hydrogen prevents social deficits and depression-like behaviors induced by low-intensity blast in mice. J Neuropathol Exp Neurol. 2018;77(9):827-836.
doi pubmed
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30-35.
doi pubmed
Yoshida A, Asanuma H, Sasaki H, Sanada S, Yamazaki S, Asano Y, Shinozaki Y, et al. H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther. 2012;26(3):217-226.
doi pubmed
Katsumata Y, Sano F, Abe T, Tamura T, Fujisawa T, Shiraishi Y, Kohsaka S, et al. The Effects of hydrogen gas inhalation on adverse left ventricular remodeling after percutaneous coronary intervention for ST-elevated myocardial infarction- first pilot study in humans. Circ J. 2017;81(7):940-947.
doi pubmed
Chen J, Zhang H, Hu J, Gu Y, Shen Z, Xu L, Jia X, et al. Hydrogen-rich saline alleviates kidney fibrosis following AKI and retains klotho expression. Front Pharmacol. 2017;8:499.
doi pubmed
Qiu P, Liu Y, Zhang J. Recent advances in studies of molecular hydrogen against sepsis. Int J Biol Sci. 2019;15(6):1261-1275.
doi pubmed
Matsuoka T, Suzuki M, Sano M, Hayashida K, Tamura T, Homma K, Fukuda K, et al. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017;83(3):469-475.
doi pubmed
Tamura T, Sano M, Matsuoka T, Yoshizawa J, Yamamoto R, Katsumata Y, Endo J, et al. Hydrogen gas inhalation attenuates endothelial glycocalyx damage and stabilizes hemodynamics in a rat hemorrhagic shock model. Shock. 2020;54(3):377-385.
doi pubmed
Li S, Liao R, Sheng X, Luo X, Zhang X, Wen X, Zhou J, et al. Hydrogen gas in cancer treatment. Front Oncol. 2019;9:696.
doi pubmed
Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, Ohta S. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016;6:18971.
doi pubmed
Tamura T, Suzuki M, Hayashida K, Kobayashi Y, Yoshizawa J, Shibusawa T, Sano M, et al. Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome. J Clin Biochem Nutr. 2020; Epub ahead of print.
doi pubmed
Kobayashi E, Sano M. Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs. PLoS One. 2019;14(10):e0222863.
doi pubmed
Sano M, Ichihara G, Katsumata Y, Hiraide T, Hirai A, Momoi M, Tamura T, et al. Pharmacokinetics of a single inhalation of hydrogen gas in pigs. PLoS One. 2020;15(6):e0234626.
doi pubmed
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.
doi pubmed

References