Abstract
BackgroundBronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.MethodsPups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.ResultsPreterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.ConclusionsPreterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.
Highlights
Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed
Preterm birth affects lung structure and function at birth, and has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on bronchopulmonary dysplasia (BPD)
Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD
Summary
Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. Antenatal steroids and surfactant supplementation have improved survival of more preterm infants with more immature lungs. This is associated with an increasing incidence of BPD, as defined by oxygen dependency at 36 weeks of life [1]. The adoption of non-invasive ventilation and lower oxygen saturation targets on the other Despite this evolution to a “new” type of BPD, respiratory disease remains an important long term consequence of preterm birth. Lung function in survivors of extreme preterm birth is significantly different from term controls at long term, even in the absence of BPD or oxygen dependency [6, 7]. Further efforts to improve the respiratory outcomes of former preterm neonates remain necessary, regardless of oxygen dependency
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