# Inhalation of hydrogen gas reduces exacerbations of acute aortic dissection in mice.
> 水素ガス吸入がマウス急性大動脈解離の増悪を抑制する


## Abstract

Acute aortic dissection (AAD) is a life-threatening vascular condition in which inflammatory processes drive disease progression and complications including rupture. Using a murine AAD model established by β-aminopropionitrile pretreatment combined with continuous angiotensin II infusion, male C57BL/6J mice were exposed to 2% H2 gas or control gas for 24 hours. H2 inhalation improved 24-hour survival and spontaneous locomotor activity without altering systolic blood pressure. Aortic rupture frequency and false lumen expansion were both reduced. Plasma IL-6 and G-CSF concentrations declined significantly, and MMP-9 and CXCL1 showed decreasing trends. Within the aortic wall, MMP-9 and CXCL1 expression—particularly in Ly-6B.2-positive regions—was diminished, and the number of Ly-6B.2-positive cells correlated positively with false lumen area. In bone marrow, the AAD-associated reduction in CD11b+Ly-6G+ neutrophils was significantly attenuated by H2 inhalation. Oxidative stress markers in the aortic wall were also reduced. These results suggest that 2% H2 gas inhalation limits AAD exacerbation through modulation of neutrophil-mediated inflammation and oxidative stress.

### Mechanism

H2 inhalation reduces circulating IL-6 and G-CSF, suppresses MMP-9 and CXCL1 expression in the aortic wall, decreases neutrophil (Ly-6B.2-positive cell) infiltration, and attenuates oxidative stress, collectively limiting false lumen expansion and aortic rupture in AAD.

## Bibliographic

- **Authors**: Iketani M, Kawata M, Ito M, Ohsawa I, Takayama K, Aokage T
- **Journal**: Life Sci
- **Year**: 2026 (2026-05-07)
- **PMID**: [42105975](https://pubmed.ncbi.nlm.nih.gov/42105975/)
- **DOI**: [10.1016/j.lfs.2026.124443](https://doi.org/10.1016/j.lfs.2026.124443)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## 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 42105975. https://h2-papers.org/en/papers/42105975
> **Source**: PubMed PMID [42105975](https://pubmed.ncbi.nlm.nih.gov/42105975/)