CONGENITAL DIAPHRAGMATIC-HERNIA - THE IMPACT OF EMBRYOLOGICAL STUDIES

In recent years, a substantial research effort within the specialty of pediatric surgery has been devoted to improving our knowledge of the natural history and pathophysiology of congenital diaphragmatic hernia s (CDH) and pulmonary hypoplasia (PH). However, the embryological back ground has remained elusive because certain events of normal diaphragm atic development were still unclear and appropriate animal models were lacking. Most authors assume that delayed or inhibited closure of the diaphragm will result in a diaphragmatic defect that is wide enough t o allow herniation of the gut into the fetal thoracic cavity. However, we feel that this assumption is not based on appropriate embryologica l observations. To clarify whether it was correct, we restudied the mo rphology of pleuroperitoneal openings in normal rat embryos. Shortly b efore, a model for CDH and PH had been established in rats using nitro fen (2,4-di-chloro-phenyl-p-nitrophenyl ether) as teratogen. We used t his model in an attempt to answer the following questions: (1) When do es the diaphragmatic defect appear? (2) Are the pleuroperitoneal canal s the precursors of the diaphragmatic defect? (3) Why is the lung hypo plastic in babies and infants with CDH? In our study we made following observations: (1) The typical findings of CDH and PH cannot be explai ned by inhibited closure of the pleuroperitoneal ''canals.'' In normal development, the pleuroperitoneal openings are always too small to al low herniation of gut into the thoracic cavity. (2) The maldevelopment of the diaphragm starts rather early in the embryonic period (5th wee k). The lungs of CDH rats are significantly smaller than those of cont rol rats at the end of the embryonic period (8th week). (3) The maldev elopment of the lungs in rats with CDH is ''secondary'' to the defect of the diaphragm. (4) The defect of the lungs is ''structural'' rather than ''functional.'' Complete spontaneous correction of these lung de fects is unlikely even after fetal intervention. (5) The ''fetal lamb model'' does not completely mimic the full picture of CDH, because the onset of the defect lies clearly in the fetal period. We believe that our rat model is better. It is especially useful for describing the a bnormal embryology of this lesion.