# Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model.
> 出血性ショックラットモデルにおける水素ガス吸入による血管内皮グリコカリックス保護と血行動態安定化


## Abstract

This study investigated the molecular mechanisms underlying the hemodynamic benefits of hydrogen gas (H2) inhalation in a rat hemorrhagic shock and resuscitation (HS/R) model. Shock was induced by lowering mean arterial pressure to 35 mmHg for 60 minutes, followed by resuscitation. H2 inhalation and xanthine oxidoreductase inhibition (XOR-I) each independently stabilized blood pressure and improved 6-hour survival rates, with additive effects observed when combined. Notably, H2 did not alter XOR enzymatic activity, indicating an XOR-independent mechanism. Plasma TNF-α and syndecan-1 levels were both reduced by H2 inhalation. When anti-TNF-α monoclonal antibody was co-administered, no further benefit from H2 was detected, suggesting that H2 acts primarily by suppressing TNF-α-mediated shedding of syndecan-1 from the endothelial glycocalyx, thereby preserving vascular integrity and hemodynamic function after resuscitation.

### Mechanism

H2 inhalation suppresses TNF-α production, thereby inhibiting syndecan-1 shedding from the endothelial glycocalyx. This preserves vascular barrier function and stabilizes hemodynamics after hemorrhagic shock, operating independently of xanthine oxidoreductase activity.

## Bibliographic

- **Authors**: Tamura T, Sano M, Matsuoka T, Yoshizawa J, Yamamoto R, Katsumata Y, et al.
- **Journal**: Shock
- **Year**: 2020
- **PMID**: [32804466](https://pubmed.ncbi.nlm.nih.gov/32804466/)
- **DOI**: [10.1097/SHK.0000000000001459](https://doi.org/10.1097/SHK.0000000000001459)
- **PMC**: [PMC7458091](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458091/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 32804466. https://h2-papers.org/en/papers/32804466
> **Source**: PubMed PMID [32804466](https://pubmed.ncbi.nlm.nih.gov/32804466/)