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Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke.

2%水素吸入による熱中症ラットの生存率改善と血管内皮グリコカリックス脱落抑制効果

animal study inhalation positive 2–4%

Abstract

Heat stroke induces severe oxidative stress and systemic inflammation, contributing to vascular endothelial glycocalyx shedding and elevated mortality. This animal study used 98 Wistar rats exposed to a 40°C, 60% humidity chamber to model heat stroke, followed by inhalation of 0%, 2%, or 4% hydrogen gas for one hour. Survival rates, glycocalyx thickness in the left ventricle, and multiple serum biomarkers were assessed. Rats receiving 2% hydrogen showed significantly improved survival and partial preservation of glycocalyx thickness. Serum concentrations of endotoxin, syndecan-1, malondialdehyde, and tumor necrosis factor-α were reduced, while superoxide dismutase activity increased. These findings indicate that 2% hydrogen inhalation confers protection against glycocalyx degradation through antioxidative and anti-inflammatory mechanisms. The 4% concentration did not demonstrate equivalent benefit, suggesting a dose-dependent response.

Mechanism

Inhalation of 2% H2 suppresses oxidative stress (reduced malondialdehyde) and inflammatory signaling (reduced TNF-α) while enhancing superoxide dismutase activity, collectively limiting enzymatic and oxidative degradation of the vascular endothelial glycocalyx.

Bibliographic

Authors
Truong SK, Katoh T, Mimuro S, Sato T, Kobayashi K, Nakajima Y
Journal
Shock
Year
2021 (2021-10-01)
PMID
34524269
DOI
10.1097/SHK.0000000000001797

Tags

Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) endothelial function (35) hydroxyl radical scavenging (352) anti-inflammatory (743) lipid peroxidation (238) oxidative stress (899) reactive oxygen species (774)

Delivery context

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

→ Evidence by delivery route

Safety notes

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

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