Persistent pulmonary hypertension (PPH) is a common consequence of many neonatal respiratory diseases. The pathophysiology of PPH remains unknown. To study PPH, a rat model of pulmonary hypoplasia was used. Lung mass and body mass were recorded and lungs were prepared for frozen section examination and stained with hematoxylin and eosin, elastin, anti-Factor Vm, and nitro blue tetrazolium to identify nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. The lungs were analyzed for air space volume, pulmonary artery wall thickness, total pulmonary arterial cross-sectional area, and density of tissue NADPH diaphorase staining. The mass of hypoplastic lungs was less than that of normal lungs (mean mass 85.93 mg vs 142.97 mg, P < 0.0001). The measured fraction of airspace volume was significantly less in hypoplastic lungs compared to controls (17.7% vs 30.8%, P < 0.0001). There was a significant difference in the pulmonary artery wall thickness ratio between the two groups (control 0.46 vs hypoplastic 0.487, P = 0.001). The arterial cross-sectional area was identical (control 1.25% vs hypoplastic 1.37%, P = 0.47). Staining density for NADPH diaphorase activity was determined using an intensity staining index (ISI). The experimental group showed increased staining for NADPH diaphorase (ISI = 54 in hypoplastic lungs vs 38 in controls, P < 0.01). Lung mass, appearance, and measured volume of airspace and tissue were all consistent with hypoplasia. In this model, arterial wall thickness was measurably greater in the hypoplastic group, while arterial cross-sectional area was not different. Staining for NADPH diaphorase showed significantly greater levels of enzyme in the hypoplastic lung. These data suggest that pulmonary hypertension in hypoplasia results in part from a biochemical. mechanism. Precise characterization of pulmonary biochemical properties may lead to improved therapies for PPH of the newborn. (C) 1995 Academic Press, Inc.
