Supplementary Material for: Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits

Background: Caffeine is a commonly used drug for apnea of prematurity. It may, however, also have a beneficial effect on bronchopulmonary dysplasia (BPD), which is the most common complication of extreme preterm birth. Objectives: To study the inflammatory, structural and functional effects of caffeine in an animal model of BPD. Methods: Preterm New Zealand-Dendermonde rabbits (gestational day 28; term 31) were randomized to three groups: normoxia-placebo (N-P), hyperoxia-placebo (H-P) and hyperoxia-caffeine (H-C). Lung function was assessed on postnatal day 5, along with airway morphometry, vascular morphometry and a score observing airway inflammation. Results: Caffeine improved lung function by increasing lung volume [mean displaced volume N-P: 40.1 ± 6 ml/kg, H-P: 27.8 ± 8 ml/kg and H-C: 34.4 ± 7 ml/kg (p 2O/ml, H-P: 4.6 ± 0.6 cm H2O/ml and H-C: 3.2 ± 0.4 cm H2O/ml (p 2O/ml, H-P: 19.2 ± 7.4 cm H2O/ml and H-C: 10.7 ± 2 cm H2O/ml (p 2O/ml, H-P: 0.054 ± 0.01 cm H2O/ml and H-C: 0.07 ± 0.013 cm H2O/ml (p Conclusion: In preterm rabbits, caffeine reduces the functional, architectural and inflammatory pulmonary changes induced by hyperoxia in the lung.