Molecular hydrogen inhalation in patients with acute cerebral ischemiaScientific Research
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
Abstract
In animal studies, the use of molecular hydrogen (H2) is considered to be quite safe and effective, showing benefits in a variety of pathological conditions, such as ischemia-reperfusion injury to the brain, heart, kidney and transplanted tissues, The same is true of traumatic and surgical injuries as well as spinal cord, intestinal and pneumonia, degenerative striatal nigra tissue and many other conditions. However, due to the older age of patients with cerebral ischemia, safety information needs to be confirmed. For the feasibility of H2 therapy in these patients, the consistency of H2 delivery by inhalation must be examined.
Methods
Hydrogen concentration (HC) in arterial and venous blood was measured by gas chromatography in 3 patients before, during and after 4% (case 1) and 3% (cases 2, 3) H2 gas inhalation while monitoring physiological parameters .For the consistency study, HC was obtained multiple times from the venous blood of 10 patients at the end of the 30-minute H2 inhalation treatment.
Results
HC gradually reached a plateau level in the blood 20 minutes after inhalation of H2, which corresponds to the levels reported in animal studies. After cessation of H2 inhalation, HC rapidly declined to 10% of the plateau levels in arterial and venous blood at approximately 6 and 18 minutes, respectively. The physiological parameters of these 3 patients were basically unchanged after the use of hydrogen. A 10-patient concordance study showed that HC was highly variable at the end of 30-minute inhalation therapy, but this inconsistency improved with more attention and encouragement.
Conclusion
Without compromising safety, inhalation of H2 at a concentration of at least 3% for 30 minutes provides sufficient HC in the blood comparable to animal values. However, there is a need to improve the consistency of H2 delivery by inhalation.
References
Glueckauf E, Kitt G: The hydrogen content of atmospheric air at ground level. Quart J Royal Met Society. 1957, 83: 522-528. 10.1002/qj.49708335808.
Levitt MD: Production and excretion of hydrogen gas in man. N Eng J Med. 1969, 281: 122-127. 10.1056/NEJM196907172810303.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007, 13: 688-694. 10.1038/nm1577.
Eckermann S, Kraft PR, Shoemaker L, Lieberson RE, Chang SD, Colohan A: Potential application of hydrogen in traumatic and surgical brain injury, stroke and Neonatal hypoxia-ischemia. Mrdical Gas Research. 2012, 2: 12-20. 10.1186/2045-9912-2-12.
Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nawashiro H: Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen as compared to Edaravone alone, A non-randamized study. Medical Gas Research. 2011, 1: 12-20. 10.1186/2045-9912-1-12.
Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nakao A: Hydrogen(H2) treatment for acute erythematous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Medical gas Research. 2012, 2: 14-10.1186/2045-9912-2-14.
Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S: Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009, 34: 501-508. 10.1038/npp.2008.95.
Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S: Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009, 64: 753-761. 10.1007/s00280-008-0924-2.
Cardinal JS, Zhan J, Wang Y, Sugimoto R, Tsung A, McCurry KR, Billar R, Nakao A: Oral administration of hydrogen water prevents chronic allograft nephropathy in rat renal transplantation. Kidney Int. 2010, 77: 101-109. 10.1038/ki.2009.421.
Perman JA, Modler S, Olson AC: Role of pH in production of hydrogen from arbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest. 1981, 67: 643-650. 10.1172/JCI110079.
Eisenmann A, Amann A, Said M, Datta B, Ledochowski M: Implementation and interpretation of hydrogen breath test. J Breath Res. 2008, 2: 1-9.
Hertzler SR, Savaiano DA, Levitt MD: Fecal hydrogen production and consumption measurements. Response to daily lactose ingestion by lactose maldigesters. Dig Dis Sci. 1997, 42: 348-353. 10.1023/A:1018822103911.
Christl SU, Murgatroyd PR, Gibson GR, Cummings JH: Production, metabolism, and excretion of hydrogen in the large intestine. astroenterology. 1992, 102: 1269-1277.
Kagaya M, Iwata M, Toda Y, Nakae Y, Kondo T: Circadian rhythm of breath hydrogen in young women. J Gastroenterol. 1998, 33: 472-476. 10.1007/s005350050117.
Henninger N, Bouley J, Nelligan JM, Sicard KM, Fisher M: Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 2007, 27: 1632-1642. 10.1038/sj.jcbfm.9600463.
Wenlan L, Qingquan C, Jie L, Ke Jian L: Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxydase in ischemic stroke. Medical Gas Research. 2011, 1: 22-30. 10.1186/2045-9912-1-22.
Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH, et al: A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke. 2005, 36: 797-802. 10.1161/01.STR.0000158914.66827.2e.
Cornet AD, Kooter AJ, Mike JL P: Supplemental oxygen therapy in medical emergencies: More harm than benefit?. Arch Intern Med. 2012, 172 (3): 289-290. 10.1001/archinternmed.2011.624.
DOI: 10.1186
Published on: 23/08/2023
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
Abstract
In animal studies, the use of molecular hydrogen (H2) is considered to be quite safe and effective, showing benefits in a variety of pathological conditions, such as ischemia-reperfusion injury to the brain, heart, kidney and transplanted tissues, The same is true of traumatic and surgical injuries as well as spinal cord, intestinal and pneumonia, degenerative striatal nigra tissue and many other conditions. However, due to the older age of patients with cerebral ischemia, safety information needs to be confirmed. For the feasibility of H2 therapy in these patients, the consistency of H2 delivery by inhalation must be examined.
Methods
Hydrogen concentration (HC) in arterial and venous blood was measured by gas chromatography in 3 patients before, during and after 4% (case 1) and 3% (cases 2, 3) H2 gas inhalation while monitoring physiological parameters .For the consistency study, HC was obtained multiple times from the venous blood of 10 patients at the end of the 30-minute H2 inhalation treatment.
Results
HC gradually reached a plateau level in the blood 20 minutes after inhalation of H2, which corresponds to the levels reported in animal studies. After cessation of H2 inhalation, HC rapidly declined to 10% of the plateau levels in arterial and venous blood at approximately 6 and 18 minutes, respectively. The physiological parameters of these 3 patients were basically unchanged after the use of hydrogen. A 10-patient concordance study showed that HC was highly variable at the end of 30-minute inhalation therapy, but this inconsistency improved with more attention and encouragement.
Conclusion
Without compromising safety, inhalation of H2 at a concentration of at least 3% for 30 minutes provides sufficient HC in the blood comparable to animal values. However, there is a need to improve the consistency of H2 delivery by inhalation.
References
Glueckauf E, Kitt G: The hydrogen content of atmospheric air at ground level. Quart J Royal Met Society. 1957, 83: 522-528. 10.1002/qj.49708335808.
Levitt MD: Production and excretion of hydrogen gas in man. N Eng J Med. 1969, 281: 122-127. 10.1056/NEJM196907172810303.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007, 13: 688-694. 10.1038/nm1577.
Eckermann S, Kraft PR, Shoemaker L, Lieberson RE, Chang SD, Colohan A: Potential application of hydrogen in traumatic and surgical brain injury, stroke and Neonatal hypoxia-ischemia. Mrdical Gas Research. 2012, 2: 12-20. 10.1186/2045-9912-2-12.
Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nawashiro H: Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen as compared to Edaravone alone, A non-randamized study. Medical Gas Research. 2011, 1: 12-20. 10.1186/2045-9912-1-12.
Ono H, Nishijima Y, Adachi N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nakao A: Hydrogen(H2) treatment for acute erythematous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Medical gas Research. 2012, 2: 14-10.1186/2045-9912-2-14.
Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S: Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology. 2009, 34: 501-508. 10.1038/npp.2008.95.
Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S: Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009, 64: 753-761. 10.1007/s00280-008-0924-2.
Cardinal JS, Zhan J, Wang Y, Sugimoto R, Tsung A, McCurry KR, Billar R, Nakao A: Oral administration of hydrogen water prevents chronic allograft nephropathy in rat renal transplantation. Kidney Int. 2010, 77: 101-109. 10.1038/ki.2009.421.
Perman JA, Modler S, Olson AC: Role of pH in production of hydrogen from arbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest. 1981, 67: 643-650. 10.1172/JCI110079.
Eisenmann A, Amann A, Said M, Datta B, Ledochowski M: Implementation and interpretation of hydrogen breath test. J Breath Res. 2008, 2: 1-9.
Hertzler SR, Savaiano DA, Levitt MD: Fecal hydrogen production and consumption measurements. Response to daily lactose ingestion by lactose maldigesters. Dig Dis Sci. 1997, 42: 348-353. 10.1023/A:1018822103911.
Christl SU, Murgatroyd PR, Gibson GR, Cummings JH: Production, metabolism, and excretion of hydrogen in the large intestine. astroenterology. 1992, 102: 1269-1277.
Kagaya M, Iwata M, Toda Y, Nakae Y, Kondo T: Circadian rhythm of breath hydrogen in young women. J Gastroenterol. 1998, 33: 472-476. 10.1007/s005350050117.
Henninger N, Bouley J, Nelligan JM, Sicard KM, Fisher M: Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 2007, 27: 1632-1642. 10.1038/sj.jcbfm.9600463.
Wenlan L, Qingquan C, Jie L, Ke Jian L: Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxydase in ischemic stroke. Medical Gas Research. 2011, 1: 22-30. 10.1186/2045-9912-1-22.
Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH, et al: A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke. 2005, 36: 797-802. 10.1161/01.STR.0000158914.66827.2e.
Cornet AD, Kooter AJ, Mike JL P: Supplemental oxygen therapy in medical emergencies: More harm than benefit?. Arch Intern Med. 2012, 172 (3): 289-290. 10.1001/archinternmed.2011.624.
