Growth of pulmonary microvasculature in ventilated preterm infants

Am J Respir Crit Care Med. 2006 Jan 15;173(2):204-11. doi: 10.1164/rccm.200506-927OC. Epub 2005 Oct 6.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blotting, Western / methods
  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / pathology
  • Cell Proliferation
  • Endothelial Cells / pathology
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Infant, Very Low Birth Weight
  • Lung / blood supply*
  • Lung / growth & development*
  • Lung / pathology
  • Lung Volume Measurements / methods
  • Male
  • Microcirculation / growth & development*
  • Microcirculation / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
  • Respiration, Artificial / methods*
  • Stillbirth
  • Time Factors


  • Platelet Endothelial Cell Adhesion Molecule-1