EFFECT OF ANTENATAL TRACHEAL OCCLUSION ON LUNG DEVELOPMENT IN THE SHEEP MODEL OF CONGENITAL DIAPHRAGMATIC-HERNIA - A MORPHOMETRIC ANALYSIS OF PULMONARY STRUCTURE AND MATURITY

The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,00 0, and the condition is associated with high mortality and morbidity, attributed principally to associated pulmonary hypoplasia. Repairing t he diaphragmatic defect by antenatal surgery has high mortality, mainl y due to premature labor. Antenatal tracheal occlusion, which is achie vable by less invasive methods, stimulates lung growth (weight and DNA ). However, its effectiveness in reversing structural acid maturationa l abnormalities and its optimal timing requires further investigation. We hypothesized that (1) antenatal tracheal occlusion performed in th e lamb model of congenital diaphragmatic hernia will stimulate lung gr owth and structural development and restore lung structure and maturit y toward normal levels by term gestation; (2) effects will be detectab le by morphometric measurements of the following parameters: lung volu me, ratio of parenchyma to nonparenchyma, volume density of connective tissue within nonparenchyma, ratio of gas exchange tissue to airspace in parenchyma, gas exchange surface area, capillary loading, alveolar /airspace density and alveolar perimeter; (3) effects will be seen in all lobes of the lung; and (4) a greater effect will be observed when tracheal occlusion is performed early rather than late in gestation. F ourteen lambs underwent CDH creation at gestation day 72-74 followed b y tracheal occlusion at day 101 (n = 7) or 129 (n = 7). They were deli vered by Cesarean section at 143 days (term = 145-149). Lungs were obt ained at autopsy, inflation fixed, divided into robes, and sampled; mo rphometric analysis was performed. Comparisons were made with previous ly reported results from control lungs of normal lambs and lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal occlusion at both times resulted in increased volumes for total lung a nd lobes, increased volume density of parenchyma and of airspace withi n parenchyma, and increased gas exchange surface areas. Normal values for gas exchange surface area density, and alveolar density and perime ter were attained and the lungs appeared more mature than non-occluded lungs. Tracheal occlusion earlier in gestation produced a greater eff ect, achieving greater than normal values for lung volumes and volume densities, whereas the capillary loading value was similar to normal l ung. Later occlusion achieved less than normal values for lung volumes and volume densities, with a reduced capillary loading value. We conc lude that antenatal tracheal occlusion is capable of reversing structu ral total lung and lobar hypoplasia and immaturity caused by CDH as de termined by morphometrically determined parameters. The effect is grea ter when tracheal occlusion is performed early rather than late in ges tation. The results are encouraging for development of treatment metho ds for humans with antenatally diagnosed CDH. (C) 1998 Wiley-Liss, Inc .