Abstract
Bronchopulmonary dysplasia (BPD) is a complex condition frequently occurring in preterm newborns, and different animal models are currently used to mimic the pathophysiology of BPD. The comparability of animal models depends on the availability of quantitative data obtained by minimally biased methods. Therefore, the aim of this study was to provide the first design-based stereological analysis of the lungs in the hyperoxia-based model of BPD in the preterm rabbit. Rabbit pups were obtained on gestation day 28 (three days before term) by cesarean section and exposed to normoxic (21% O2, n = 8) or hyperoxic (95% O2, n = 8) conditions. After seven days of exposure, lung function testing was performed, and lungs were taken for stereological analysis. In addition, the ratio between pulmonary arterial acceleration and ejection time (PAAT/PAET) was measured. Inspiratory capacity and static compliance were reduced whereas tissue elastance and resistance were increased in hyperoxic animals compared with normoxic controls. Hyperoxic animals showed signs of pulmonary hypertension indicated by the decreased PAAT/PAET ratio. In hyperoxic animals, the number of alveoli and the alveolar surface area were reduced by one-third or by approximately 50% of control values, respectively. However, neither the mean linear intercept length nor the mean alveolar volume was significantly different between both groups. Hyperoxic pups had thickened alveolar septa and intra-alveolar accumulation of edema fluid and inflammatory cells. Nonparenchymal blood vessels had thickened walls, enlarged perivascular space, and smaller lumen in hyperoxic rabbits in comparison with normoxic ones. In conclusion, the findings are in line with the pathological features of human BPD. The stereological data may serve as a reference to compare this model with BPD models in other species or future therapeutic interventions.
Highlights
Bronchopulmonary dysplasia (BPD) is a chronic human lung disease associated with preterm birth
Bronchopulmonary dysplasia (BPD) is a complex condition frequently occurring in preterm newborns, and different animal models are currently used to mimic the pathophysiology of BPD
The average body weight did not differ between the two experimental groups after 7 days of exposure to hyperoxic or normoxic air and was 50 g (±4.9 g) for the normoxia-exposed pups and 49 g (±9 g) for the hyperoxiaexposed pups
Summary
Bronchopulmonary dysplasia (BPD) is a chronic human lung disease associated with preterm birth. With the possibility of treating preterm babies with exogenous surfactant, this form of BPD (“old BPD”) has decreased; the progress in neonatal care has helped to keep alive very immature neonates, born between gestation weeks 24 and 28 [2]. At this stage, lung development is incomplete and needs to progress to gain full functional capacity, while at the same time, the immature lung is required to work as a gas exchanger. Due to the chronic nature of BPD, children with this disease are affected lifelong by the consequences of disrupted lung development, and therapeutic approaches are needed to promote extrauterine lung development in extremely preterm newborns [2, 6,7,8]
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