Molecular hydrogen attenuates sepsis-induced cardiomyopathy in mice by promoting autophagy.
水素吸入がオートファジー促進を介してマウスの敗血症性心筋症を軽減する
Abstract
Sepsis-induced cardiomyopathy (SIC) affects 40–60% of septic patients and substantially elevates mortality risk. Using a cecal ligation and puncture (CLP) mouse model, this study investigated whether 2% H2 inhalation confers cardiac protection and explored the underlying autophagic mechanism. C57BL/6J male mice were allocated to sham, sham+H2, CLP, and CLP+H2 groups. H2-treated septic mice showed significantly improved 7-day survival, reduced myocardial inflammation, lower serum cardiac troponin I (cTnI) levels, enhanced autophagy flux, and altered mitophagy-related protein expression. To confirm the autophagic pathway, the autophagy inhibitor bafilomycin A1 (BafA1, 1 mg/kg intraperitoneally) was administered post-CLP. BafA1 co-treatment reversed the H2-associated improvements in survival, myocardial injury scores, and cTnI levels, indicating that autophagy flux is essential for the cardioprotective action of H2 in sepsis.
Mechanism
H2 inhalation promotes autophagy flux and mitophagy in cardiac tissue, thereby reducing myocardial inflammation and injury in septic mice. Blockade of autophagy with bafilomycin A1 abolished these protective effects, confirming the autophagic pathway as the key mediator.
Bibliographic
- Authors
- Cui Y, Li Y, Meng S, Song Y, Xie K
- Journal
- BMC Anesthesiol
- Year
- 2024 (2024-02-23)
- PMID
- 38395800
- DOI
- 10.1186/s12871-024-02462-4
- PMC
- PMC10885652
Tags
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.
Safety notes
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