Preserved Acute Pulmonary Endothelial Homeostasis with Hydrogen Gas Inhalation After Neonatal Hypoxia-Ischemia...

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.