06/02/2006
Pulmonary Microvasculature of Ventilated Preterm Infants Undergoes Active Angiogenesis

Lung microvascular network showed expansion, rather than reduction, after mechanical ventilation

Preterm newborns treated with ventilation and supplemental oxygen frequently develop bronchopulmonary dysplasia (BPD), a chronic lung disease of newborn infants associated with significant mortality and morbidity.

Autoptic studies demonstrated that postsurfactant BPD is an arrest in alveolar development, resulting in lungs with large and simplified airspaces. This leads to a global reduction in alveolar number and gas-exchange surface area. Since proper formation of the pulmonary microvasculature is required for normal alveolar development, it is believed that this histological pattern may be caused by ventilation-induced disruption of the normal lung development in newborns born during the late canalicular stage (23–27 weeks of gestation), but these findings need further elucidations.

A comprehensive analysis (Am J Respir Crit Care Med 2006 Jan 15;173(2):204-11, PubMed ) of the early and late effects of mechanical ventilation on microvascular development in the lungs of preterm infants was performed on postmortem lung samples. They were collected from ventilated preterm infants who died between 23 and 29 weeks (“short-term ventilated”) or between 36 and 39 weeks (“long-term ventilated”) corrected postmenstrual age. Results were compared with age-matched or stillborn infants. Microvascular growth was studied by various experimental methods, such as histological analysis, quantitative stereologic and immunohistochemical double-libelling techniques.

Lungs of long-term ventilated infants showed a 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 anti-platelet endothelial cell adhesion molecule (PECAM-1) 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 observation that ventilation induces proliferation of the pulmonary microvasculature is in contrast with a prevailing notion, based on more limited experimental analysis, that BPD is characterized by disruption of microvascular development. This study demonstrated that the postcanalicular pulmonary circulation may undergo angiogenesis, if stimulated by factors associated with prolonged mechanical ventilation. The expansion of the pulmonary microvasculature was nearly proportional to the growth of the air-exchanging parenchyma. However, the capillary network in ventilated lungs was found to retain the primitive vascular pattern of canalicular/saccular lungs, characterized by simplified, non-branching vessels. This could lower the efficiency of gas exchange in the expanding parenchyma.

In conclusion, this study reported that the pulmonary microvasculature of ventilated preterm infants undergoes active angiogenesis, proportional to the degree of expansion of the air-exchanging parenchyma. Even if this analysis is performed in infants with lethal forms of BPD, it is likely that angiogenesis may also occur in survivors of BPD. These findings challenge the widely accepted paradigm that ventilation-induced disruption of microvascular development in immature lungs can contribute to BPD disease in preterm infants.

Top