Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs

Premature birth is a major cause of pediatric morbidity and mortality. Bronchopulmonary dysplasia (BPD) is a severe consequence of extreme prematurity, leading to lung growth alterations and long-lasting developmental effects. The pathogenesis of BPD is multi-factorial, including mechanical ventilation, hyperoxia, and inflammation as the main drivers of its development. Currently, there is no treatment for BPD. In this study, a feasible and reproducible new neonatal piglet model of acute lung injury (ALI), mimicking the clinical stimuli faced by the human preterm lung, is presented. The multi-hit ALI neonatal piglet model - combining surfactant depletion, hyperoxia, high pressure-ventilation, and intratracheal lipopolysaccharide (LPS) administration results in impaired oxygenation, perturbed lung function, inflammation with neutrophil infiltration, and histological lung injury. Its main advantages are using the harmful stimuli known to drive BPD pathogenesis and its low maintenance. It generates high-fidelity ALI, meeting the American Thoracic Society ALI criteria. Large animal models, such as this piglet model, are critical to understanding early pathogenic factors, identifying therapeutic targets, and facilitating clinical translation to patients.