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Updated: Aug 15, 2026
Transcutaneous Microcirculatory Imaging in Preterm Neonates
Published on: December 31, 2015
Growth of pulmonary microvasculature in ventilated preterm infants
Monique E De Paepe1, Quanfu Mao, Jessica Powell
1Women and Infants Hospital, Department of Pathology, 101 Dudley Street, Providence, RI 02905, USA. mdepaepe@wihri.org
Insights
Ventilated preterm infants show increased pulmonary microvascular growth, challenging the idea of disrupted microvascular development in bronchopulmonary dysplasia (BPD). This suggests angiogenesis, not arrest, is key in BPD lung development.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Vascular Biology
Background:
- Bronchopulmonary dysplasia (BPD) is often associated with decreased capillary density in infant lungs.
- This has led to the prevailing view that microvascular development is disrupted in BPD.
Purpose of the Study:
- To comprehensively analyze the early and late effects of mechanical ventilation on pulmonary microvascular growth in preterm infants.
- To investigate the impact of ventilation on microvascular development in the context of BPD.
Main Methods:
- Postmortem lung samples from ventilated preterm infants (23-39 weeks corrected postmenstrual age) and controls were analyzed.
- Quantitative stereology, immunohistochemistry (PECAM-1), endothelial cell proliferation assays (Ki67), and Western blotting were employed.
Main Results:
- Long-term ventilated infants exhibited a twofold increase in air-exchanging parenchyma volume and a 60% increase in microvascular endothelial volume compared to controls.
- Pulmonary PECAM-1 protein levels were 60% higher in ventilated lungs, linked to increased endothelial cell proliferation.
- The microvasculature in ventilated lungs showed immature, saccular architectural patterns.
Conclusions:
- Ventilated preterm infants demonstrate significant pulmonary microvascular angiogenesis, proportional to lung parenchyma growth.
- These findings challenge the established paradigm of microvascular growth arrest as a primary pathogenic factor in BPD.
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.
