Growth of pulmonary microvasculature in ventilated preterm infants.
BACKGROUND
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.


METHODS
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.


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.
De Paepe
Monique E
ME
Women and Infants Hospital, Department of Pathology, 101 Dudley Street, Providence, RI 02905, USA. mdepaepe@wihri.org
Mao
Quanfu
Q
Powell
Jessica
J
Rubin
Sam E
SE
DeKoninck
Philip
P
Appel
Naomi
N
Dixon
Meredith
M
Gundogan
Füsun
F
D015153:Blotting, Western / Q000379:methods; D001997:Bronchopulmonary Dysplasia / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008168:Lung / Q000098:blood supply* / Q000254:growth & development* / Q000473:pathology; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000254:growth & development* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D012121:Respiration, Artificial / Q000379:methods*; D050497:Stillbirth; D013997:Time Factors
D019408:Platelet Endothelial Cell Adhesion Molecule-1