Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age

Mar Janna Dahl, Sydney Bowen, Toshio Aoki, Andrew Rebentisch, Elaine Dawson, Luke Pettet, Haleigh Emerson, Baifeng Yu, Zhengming Wang, Haixia Yang, Chong Zhang, Angela P. Presson, Lisa Joss-Moore, Donald Null, Bradley A. Yoder, Kurt H. Albertine

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls (P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa (P < 0.007 and P < 0.001, respectively), and lower radial alveolar count (P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.

Original languageEnglish (US)
Pages (from-to)L816-L833
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number5
DOIs
StatePublished - Nov 1 2018

Keywords

  • Alveolar capillary growth
  • Alveolar formation
  • Bronchopulmonary dysplasia
  • Lung development
  • Neonatal chronic lung disease

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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  • Cite this

    Dahl, M. J., Bowen, S., Aoki, T., Rebentisch, A., Dawson, E., Pettet, L., Emerson, H., Yu, B., Wang, Z., Yang, H., Zhang, C., Presson, A. P., Joss-Moore, L., Null, D., Yoder, B. A., & Albertine, K. H. (2018). Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age. American Journal of Physiology - Lung Cellular and Molecular Physiology, 315(5), L816-L833. https://doi.org/10.1152/ajplung.00249.2018