Growth of pulmonary microvasculature in ventilated preterm infants

ME De Paepe, Q Mao, J Powell, SE Rubin… - American journal of …, 2006 - atsjournals.org
ME De Paepe, Q Mao, J Powell, SE Rubin, P DeKoninck, N Appel, M Dixon, F Gundogan
American journal of respiratory and critical care medicine, 2006atsjournals.org
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 …
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.
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