Aspirin Therapy Enhances Lung Alveolarization in Newborn Pups Exposed to Neonatal Hyperoxia

Abstract

Preterm infants with prolonged oxygen exposure are at risk of developing Bronchopulmonary Dysplasia (BPD). BPD is characterized by impairment of lung development and associated with inflammation. Aspirin is a cyclooxygenase inhibitor that disrupts pro-inflammatory pathways. We tested the hypothesis that aspirin therapy will improve lung function and growth following newborn hyperoxia exposure. Newborn mice were exposed to room air (RA) or >95% O2 and injected with vehicle (PBS) or 5 mg/kg aspirin (ASA) for 7 days. On day 7, O2 mice were returned to RA. Pulmonary function tests were performed on day 28 using the SCIREQ Flexivent system (n=9–11). Lungs were formalin fixed and paraffin embedded, and lung sections were H&E stained (n=3). Morphometric analysis was performed using Image Pro software. Total lung capacity (relative to body weight) was greater in PBS/O2 than PBS/RA and ASA/RA mice (78.20 ml/kg vs 50.49 ml/kg and 48.49 ml/kg, p<0.01). However, mice that received ASA during O2 exposure had lower total lung capacity (70.46 ml/kg, p<0.01). Alveolar number (per high power field) was greater in ASA/O2 mice than in the PBS/O2 mice (46 vs 69, p<0.05). Decreased total lung capacity was associated with an increase in alveolar number. Aspirin may be a beneficial therapy for preterm infants who are at risk of developing BPD and could improve long term lung development and growth.