MORPHOMETRIC ANALYSIS OF PULMONARY DEVELOPMENT IN THE SHEEP FOLLOWINGCREATION OF FETAL DIAPHRAGMATIC-HERNIA

Congenital diaphragmatic hernia (CDH) in humans is relatively common a nd associated with high mortality attributed mainly to pulmonary hypop lasia. Previous animal models have induced CDH late in gestation, in c ontrast to the human situation, and only limited morphometric analyses have been reported. We undertook early surgical creation of CDH in fe tal lambs, days 72-74 of gestation (n = 8), with unoperated lambs (n = 8) as controls. At 143 days (term = 245-149) a cesarean section was p erformed and the lungs were obtained, inflation fixed, divided into lo bes, and processed for morphometry. In the CDH group the total lung vo lumes (51.3 mL compared to 223.8 mL) and gas exchange surface areas (5 .85 m(2) versus 26.43 m(2) ) were less than one quarter of control val ues. Capillary loading was reduced from 0.3 mL/m(2) in controls to 0.1 2 mL/m(2) in CDH and parenchymal volume reduced from 77% in controls t o 57% in CDH. Within parenchyma, gas exchange tissue volume was increa sed in C=DH (66%) compared with controls (50%). CDH lungs had primitiv e air sacs/alveoli that were small (perimeter 83 mu m) and more numero us (1321 per mm(2)) than in controls (perimeter 132 mu m, 504 per mm(2 )). The left lung and left upper lobe were affected nest. Induction of CDH in the lamb at this early age results in quantifiable, reproducib le pulmonary hypoplasia from which comparisons can be made with the hu man condition.