Pulmonary vascular findings in preterm infants with bronchopulmonary dysplasia and cor pulmonale – a quantitative morphological analysis
Introduction: In Bronchopulmonary Dysplasia (BPD) the immature lung is damaged by ventilatory injury and oxygen toxicity, leading to severe fibrosis and to an arrest in alveolarisation in the lung of these infants. Chronic cor pulmonale is one of the leading causes of death in these patients. In the human little is known, whether an – out of proportion – reduction in peripheral pulmonary vascularisation would explain for the severe cor pulmonale observed in these patients.
Patients and Methods: Autopsy study performed at the Dept. of Paed. Pathology of the Charité Berlin (1990–1993) on 5 preterm infants; 27 (26–28) weeks of gestation (median (range)), birthweight 808 (560–1135g), survival 7.5 (2.5–13) months. Two infants that died acutely without mechanical ventilation or known lung disease (age 2 and 5 months) were used as controls. Mikroangiographic analysis of lung tissue and quantitative morphometric analysis of the lung structures (serial sections, more than 230.000 point measurements) was performed. Results: Cor pulmonale with increased ratio of right ventricle to left ventricle+interventricular septum muscle mass was present in 3/5 patients. The preterm infant surviving 2 months showed a considerable reduction in number of pulmonary arteries of D=75–750µm (2,9 [1,3–4,4] % vs. 6,3 [1,7–9,1] of measured points; p=0.010 Mann-Whitney) which was confirmed by microangiography. The four other patients surviving 5–13 months showed no difference with respect to the number of their pulmonary arteries compared with the control. Muscularisation of pulmonary arteries was increased in the peripheral arteries (D=25–75µm). Connective tissue proportion was increased in most patients. Conclusion: At 26–28 weeks of gestation the lung is in the saccular stage. In utero the fetal lung growths by low oxygen concentrations. After extremely preterm birth the lung is exposed to much higher oxygen concentration even in room air – too high for extremely preterm infants. The subsequent „relative hyperoxia“ lead to a decrease in hypoxia-inducible factor (HIF) and its products, such as Vascular Endothelial Growth Factor (VEGF) besides the stop in alveolarisation leading also to arrest in vascularisation. However vascular damage seems not to be out of proportion in most long term survivors. These data argue for a considerable role of functional and vasoconstrictive factors in the pathogenesis of cor pulmonale in these infants.