Currently, several animal models are used in BPD research to mimic parts of the pathophysiological sequelae of human preterm birth. įor these purposes, preclinical experiments addressing the pathophysiology of arrested lung development and the effects of new therapeutic interventions are essential. In addition, 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. In order to distinguish this form from the previously known condition, it has been termed “new BPD.” The pathophysiology of the new BPD, in particular, the mechanisms by which alveolarization is halted, is still not fully understood. As a result, lung development gets disrupted which is characterized by a decrease in alveolarization and (micro-)vascular maturation as well as interstitial changes, including deposition of fibrotic tissue. The conditions for further lung development are aggravated by perinatal inflammation/infection, mechanical ventilation, and oxygen supply.
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. With the possibility of treating preterm babies with exogenous surfactant, this form of BPD (“old BPD”) has decreased however, the progress in neonatal care has helped to keep alive very immature neonates, born between gestation weeks 24 and 28. In the early days, BPD was described to be the result of a combination of respiratory distress syndrome and the effects of therapeutic interventions, including ventilation and oxygen supply. The stereological data may serve as a reference to compare this model with BPD models in other species or future therapeutic interventions.īronchopulmonary dysplasia (BPD) is a chronic human lung disease associated with preterm birth. In conclusion, the findings are in line with the pathological features of human BPD. Nonparenchymal blood vessels had thickened walls, enlarged perivascular space, and smaller lumen in hyperoxic rabbits in comparison with normoxic ones. Hyperoxic pups had thickened alveolar septa and intra-alveolar accumulation of edema fluid and inflammatory cells. However, neither the mean linear intercept length nor the mean alveolar volume was significantly different between both groups. 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. Hyperoxic animals showed signs of pulmonary hypertension indicated by the decreased PAAT/PAET ratio. Inspiratory capacity and static compliance were reduced whereas tissue elastance and resistance were increased in hyperoxic animals compared with normoxic controls. In addition, the ratio between pulmonary arterial acceleration and ejection time (PAAT/PAET) was measured. After seven days of exposure, lung function testing was performed, and lungs were taken for stereological analysis. Rabbit pups were obtained on gestation day 28 (three days before term) by cesarean section and exposed to normoxic (21% O 2, n = 8) or hyperoxic (95% O 2, n = 8) conditions. 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.
The comparability of animal models depends on the availability of quantitative data obtained by minimally biased methods. 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.