Growth of Pulmonary Microvasculature in Ventilated Preterm Infants

• Published in: American journal of respiratory and critical care medicine Vol. 173; no. 2; pp. 204 - 211
• Main Authors: De Paepe, Monique E, Mao, Quanfu, Powell, Jessica, Rubin, Sam E, DeKoninck, Philip, Appel, Naomi, Dixon, Meredith, Gundogan, Fusun
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.01.2006; American Lung Association; American Thoracic Society
• Subjects: Age; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Autopsies; Biological and medical sciences; Blotting, Western - methods; Bronchopulmonary Dysplasia - mortality; Bronchopulmonary Dysplasia - pathology; Cell adhesion & migration; Cell growth; Cell Proliferation; E. Pediatrics and Lung Development; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Endothelial Cells - pathology; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive care medicine; Lung - blood supply; Lung - growth & development; Lung - pathology; Lung diseases; Lung Volume Measurements - methods; Lungs; Male; Medical sciences; Microcirculation - growth & development; Microcirculation - pathology; Newborn babies; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Pneumology; Premature babies; Proteins; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Respiration, Artificial - methods; Stillbirth; Time Factors; Ventilators; Human; Premature; Lung disease; Intensive care; chronic lung disease of prematurity; Respiratory disease; Chronic disease; neonatal lung disease; Newborn diseases; Newborn; Prematurity; Bronchus disease; Bronchopulmonary dysplasia; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200506-927OC

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