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Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age
Mar Janna Dahl1, Sydney Bowen1, Toshio Aoki1
1Division of Neonatology, Department of Pediatrics, University of Utah , Salt Lake City, Utah.
American Journal of Physiology. Lung Cellular and Molecular Physiology
|September 14, 2018
Summary
Former-preterm lambs supported by mechanical ventilation (MV) show persistent alveolar simplification, indicating impaired lung development. This new ovine model helps study bronchopulmonary dysplasia pathogenesis and potential treatments.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Animal Models
Background:
- Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth and mechanical ventilation (MV).
- Alveolar simplification is a key pathological feature of BPD, but its long-term consequences due to developmental immaturity and injury are poorly understood.
- Lack of suitable animal models has hindered research into the mechanisms of impaired alveolar development.
Purpose of the Study:
- To establish and validate a novel ovine model of former-preterm lambs to investigate persistent alveolar simplification.
- To test the hypothesis that moderate preterm birth followed by MV leads to lasting deficits in alveolar development.
- To provide a platform for studying the pathogenesis of BPD and identifying therapeutic targets.
Main Methods:
- Moderately preterm lambs (~85% gestation) received MV for approximately 6 days before weaning.
- Former-preterm lambs were assessed at corrected postnatal ages (cPNA) equivalent to 1-2 years and ~6 years in humans.
- Alveolar structure was quantified using morphometric and stereological methods, comparing former-preterm lambs to age-matched, unventilated term controls.
Main Results:
- Former-preterm lambs exhibited significantly thicker distal airspace walls at both 2 and 5 months cPNA (P < 0.001 and P < 0.009).
- A lower volume density of secondary septa was observed in former-preterm lambs at both time points (P < 0.007 and P < 0.001).
- Radial alveolar counts were significantly reduced in former-preterm lambs compared to controls (P < 0.003 and P < 0.020), with no sex-specific differences detected.
Conclusions:
- Moderate preterm birth and short-term MV significantly impede the completion of alveolarization in lambs.
- The developed ovine model demonstrates persistent alveolar simplification, mirroring key aspects of BPD.
- This model offers a valuable tool for future research into the mechanisms underlying impaired lung development and for testing novel interventions.
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