Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung biopsies.

Pulmonary arterial structure was examined in lung biopsies from 26 children with severe pulmonary hypertensive congenital heart disease, aged 2 months-18 years, in whom the mean pulmonary arterial pressure was 55 (range 35-105) mmHg, using light, transmission, and scanning electron microscopy. Qualitative and quantitative techniques were applied and findings compared with those in age-matched controls. At 2 months, the smooth muscle cells showed hyperplasia, hypertrophy (mean cell diameter increased, P less than 0.001), and accelerated differentiation. In all pulmonary hypertensive cases aged less than 6 months, the contractile myofilament concentration was similar to the normal concentration at 6 months. Medial connective tissue was excessive for age. Smooth muscle cells within the intima (intimal proliferation) were first seen at 7 months, lying beneath a new internal elastic lamina. They showed a reduction in myofilament concentration in the more fibrotic lesions. In all cases, endothelial cells were abnormally thick (P less than 0.001) and elongated. Cytoskeletal remodelling was indicated by an increase in micro- and intermediate filament volume density (P less than 0.05 for both). The severity of endothelial damage was related to vessel size and position in the arterial pathway. These findings indicate that pulmonary vascular disease begins at or soon after birth with abnormal pulmonary vascular remodelling which leads to obliterative pulmonary vascular disease.