Caffeine Protects Newborn Rat Lungs Against the Effects of Hyperoxia and Intra‐Amniotic Enterotoxin

Introduction Bronchopulmonary dysplasia (BPD) has a multifactorial etiology with prenatal and/or postnatal factors contributing to the pathogenesis, and there is no completely effective treatment to prevent or treat this condition. Our objective was to evaluate the effects of caffeine treatment in two BPD‐like rat models using prenatal and postnatal factors. Methods In a BPD‐like model induced by a prenatal factor, endotoxin (ETX) or saline was administered to pregnant rats by intra‐amniotic (i.a.) injection on day 20 of pregnancy, and pups were delivered by cesarean section at term (day 22). On the other hand, for a BPD‐like model induced by a postnatal factor, the pups were maintained in hyperoxia (80%–85%) (HYP) or normoxia (room air) for 14 days after natural birth. In both models, caffeine (20 mg/kg) was administered every other day until postnatal day 14. On postnatal day 14, we assessed lung function (peak‐inspiratory‐pressure, compliance), lung structure (radial‐alveolar‐count, mean‐linear‐intercept, pulmonary‐vessel‐density), and pulmonary hypertension. Result The effects of i.a. ETX or HYP were evident in neonatal rats not receiving treatment, these animals showing impaired lung function and lung structure and developing pulmonary hypertension compared to results after i.a. saline administration or normoxia. Postnatal caffeine administration was associated with significantly better outcomes in terms of lung compliance, alveolarization, lung vascular growth, and pulmonary hypertension. Conclusion In a BPD‐like model induced by prenatal (i.a. ETX) or postnatal (HYP) factors, caffeine administration preserved lung function and structure and prevented pulmonary hypertension. These findings confirm that caffeine (the drug most commonly prescribed in neonatal care units) may provide an effective strategy for BPD prevention when prenatal or postnatal factors are involved.