Hyperoxia exposure disrupts alveolar development and cardiopulmonary transition in preterm pigs

Aim Bronchopulmonary dysplasia (BPD) remains a major cause of chronic lung disease following preterm birth. We aimed to establish a normobaric hyperoxia-induced preterm pig model that reflects respiratory and cardiovascular consequences of BPD. Methods Preterm piglets (n=18) were delivered by caesarean section at gestational day 106 and exposed either to sustained hyperoxia (85% O₂) or ambient air for 94 hours. Data on echocardiography, pulmonary arterial pressure, and detailed lung and heart histopathology were collected. Results There was clear structural lung injury in hyperoxia-exposed piglets, with increased septal thickness, reduced alveolar density, higher mean linear intercepts and more alveolar necrosis (all p<0.05). Echocardiography revealed a higher prevalence of persistent ductus arteriosus (55.6% in BPD vs. 12.5% in controls; p=0.091). Histology showed right ventricular cardiomyocyte hyperplasia and hypertrophy in hyperoxia-exposed pigs, yet pulmonary arterial pressure was unaffected. Conclusion The preterm pig model recapitulates key physiological and structural hallmarks of "new BPD" and the broader chronic lung disease of prematurity. This model represents a promising platform for investigating mechanisms and interventions in preterm infants at risk of BPD.