Pathophysiology of congenital diaphragmatic hernia XVI: Elevated pulmonary collagen in the lamb model of congenital diaphragmatic hernia

The pathophysiologic features of congenital diaphragmatic hernia (CDH) include pulmonary hypoplasia, pulmonary hypertension, surfactant deficiency, and decreased pulmonary compliance. When the surfactant deficiency is corrected using exogenous surfactant therapy, the pulmonary compliance improves, but does not reach normal values. Quasistatic saline pressure-volume measurements, which eliminate the air-liquid interface, confirm that CDH lungs are intrinsically less compliant than control lungs. The authors hypothesized that this abnormal lung compliance results from elevated concentrations of collagen and/or elastin in the lung. Therefore, they measured the collagen and elastin concentrations in CDH and control lung tissue. Also measured was the collagen concentration in the kidney, intestine, and dissected third-generation arterioles, venules, and bronchioles, to characterize further the pathology of CDH. The CDH model was created on the left side of fetuses in pregnant ewes at 80 days' gestation. The fetuses were delivered and killed at 140 days (full term, 145). The concentrations of collagen (as hydroxyroline), elastin, DNA, and total protein were measured using standard techniques. Although there was significantly more collagen per gram of lung tissue in the CDH lungs (1.334 mg/g v 0.885 mg/g in the controls) the elastin concentrations were not different. The elevated collagen concentration was not associated specifically with the conducting airways or vasculature. The collagen concentrations in CDH kidneys and intestines were the same as those of controls. The DNA/total protein ratios in the CDH and control lungs were identical. The results suggest that the elevated collagen concentration was present only in the lungs of CDH lambs, and that it was not attributable to atrophy or hypertrophy of the lungs. Thus, increased collagen in the lung parenchyma may be responsible for the intrinsic stiffness and decreased compliance of the CDH lungs.