Hydrogen Gas Inhalation Keeps Newborn Lungs Safe After Oxygen Deprivation
- Authors
- Takayuki Yokota, Masumi Iketani, Toui Tsuchiya, Kosuke Sakamoto, Yasuhiro Nakao, Tsutomu Mitsuie, Eri Inoue, Kota Inoue, Tomoaki Kusaka, Takayuki Wakabayashi, Kosuke Koyano, Takanori Miki, Masaki Ueno, Shinji Nakamura, Takashi Kusaka
- Journal
- Biomedicines
- Year
- 2026
- DOI
- 10.3390/biomedicines14081707
- Study Type
- Pig
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Neonatal hypoxic-ischemic encephalopathy
- Body System
- Respiratory system
TL;DR
Six hours of hydrogen inhalation did not worsen pulmonary endothelial activation or respiratory function after neonatal hypoxic-ischemic injury, supporting its short-term pulmonary safety in this piglet model.
Key Finding
Hydrogen gas inhalation did not worsen lung inflammation or impair respiratory function in newborn piglets after oxygen-deprivation injury, despite a higher accumulation of neutrophils in the lungs.
Summary
This study looked at whether inhaling hydrogen gas (H2) might cause lung inflammation or breathing problems in newborn piglets after a hypoxic-ischemic injury (a condition where the brain and body are deprived of oxygen and blood flow). Researchers measured markers of lung inflammation, neutrophil counts (immune cells that respond to injury), and breathing function in piglets treated with H2 versus those left untreated. H2-treated piglets had more neutrophils in their lungs, but showed no signs of increased inflammation markers or worsened breathing. The higher neutrophil counts appeared to be related to improved blood flow through the lungs rather than harmful inflammation.
Practical Takeaway
This animal study suggests that inhaled hydrogen gas may be acutely safe for lung function in a neonatal injury setting, but these findings are from piglets and cannot be directly applied to humans. Early evidence indicates that H2 inhalation does not appear to trigger harmful lung inflammation, though much more research — including human trials — is needed before any conclusions can be drawn for clinical use.
Abstract
Background/Objectives: Hydrogen gas (H2) inhalation has shown neuroprotective effects in neonatal hypoxic-ischemic models. However, its impact on pulmonary endothelial activation and respiratory function after hypoxic-ischemic insult remains unclear. This study investigated whether H2 inhalation augments pulmonary endothelial activation or impairs pulmonary function during the acute phase after neonatal hypoxic-ischemic injury. Methods: Sixteen newborn Camborough® piglets within 24 h of birth were subjected to hypoxic-ischemic insult and randomized to an untreated group (HI, n = 8) or an H2-treated group (HI-H2, n = 8). The HI-H2 group received 2.1-2.7% H2 for 6 h. Pulmonary ICAM-1 and inducible nitric oxide synthase (iNOS) expression were assessed by immunofluorescence, lung neutrophils were quantified histologically, and pulmonary function was evaluated using arterial blood gases, oxygen index, and alveolar-arterial oxygen difference. The relationship between lung neutrophil counts and right ventricular cardiac output was also examined. Results: H2 inhalation did not increase pulmonary ICAM-1 expression or iNOS induction compared with untreated animals. Although lung neutrophil counts were significantly higher in the HI-H2 group, pulmonary gas exchange remained preserved, with no significant differences in arterial blood gases, oxygen index, or alveolar-arterial oxygen difference. Lung neutrophil counts were positively correlated with right ventricular cardiac output, suggesting that enhanced pulmonary perfusion may contribute to neutrophil redistribution rather than inflammatory recruitment. Conclusions: H2 inhalation preserved pulmonary endothelial homeostasis without impairing respiratory function during the acute phase after neonatal hypoxic-ischemic insult. The observed increase in lung neutrophils was not accompanied by evidence of endothelial activation or deterioration of gas exchange, supporting the acute pulmonary safety of H2 inhalation while suggesting that neutrophil accumulation may, at least in part, reflect hemodynamic redistribution rather than injurious inflammatory infiltration.