Growth of pulmonary microvasculature in ventilated preterm infants

Monique E De Paepe, Quanfu Mao, Jessica Powell, Sam E Rubin, Philip DeKoninck, Naomi Appel, Meredith Dixon, Füsun Gundogan

Research output: Contribution to journalArticleAcademicpeer-review

172 Citations (Scopus)

Abstract

RATIONALE: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD.

OBJECTIVE: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants.

METHODS: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels.

MEASUREMENTS: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels.

MAIN RESULTS: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern.

CONCLUSIONS: The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.

Original languageEnglish
Pages (from-to)204-11
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume173
Issue number2
DOIs
Publication statusPublished - 15 Jan 2006
Externally publishedYes

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