# Acoustic hydrogen delivery to treat PANoptosis induced by myocardial ischemia/reperfusion injury in rats.
> 超音波トリガー型水素内包脂質マイクロバブルによる心筋虚血再灌流傷害におけるPANoptosis抑制


## Abstract

A lipid microbubble system loaded with molecular hydrogen (H₂-MBs, diameter 0.92 ± 0.03 µm, concentration ~1.14 × 10⁹ bubbles/mL) was engineered to enable ultrasound-targeted microbubble destruction (UTMD)-mediated spatiotemporal H₂ release. In a rat myocardial ischemia/reperfusion (MIR) model, intravenous administration of H₂-MBs combined with UTMD improved cardiac ejection fraction and fractional shortening, reduced infarct area, and lessened histological damage. The H₂-MBs also supported real-time contrast-enhanced ultrasound imaging. Mechanistic investigation demonstrated that locally released H₂ suppressed H₂O₂-driven PANoptosis by simultaneously downregulating pyroptosis markers (cleaved caspase-1, GSDMD), apoptosis markers (cleaved caspase-3/8, Bax/Bcl-2 ratio), and necroptosis mediators (p-RIPK1, p-RIPK3, p-MLKL). This image-guided gas delivery platform offers a strategy for coordinated modulation of programmed inflammatory cell death in MIR injury.

### Mechanism

Ultrasound-triggered local H₂ release suppresses H₂O₂-induced PANoptosis by concurrently downregulating pyroptosis effectors (cleaved caspase-1, GSDMD), apoptosis regulators (cleaved caspase-3/8, Bax/Bcl-2 ratio), and necroptosis mediators (p-RIPK1, p-RIPK3, p-MLKL), thereby reducing programmed inflammatory cell death in ischemia-reperfused myocardium.

## Bibliographic

- **Authors**: Wang SP, Li CY, Wei ZJ, Tang C, Wang Y, Yan F, et al.
- **Journal**: Biomater Adv
- **Year**: 2026
- **PMID**: [41671925](https://pubmed.ncbi.nlm.nih.gov/41671925/)
- **DOI**: [10.1016/j.bioadv.2026.214770](https://doi.org/10.1016/j.bioadv.2026.214770)
- **Study type**: animal study
- **Delivery route**: injection / infusion
- **Effect reported**: positive

## Delivery context

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).

## Safety notes

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41671925. https://h2-papers.org/en/papers/41671925
> **Source**: PubMed PMID [41671925](https://pubmed.ncbi.nlm.nih.gov/41671925/)