The effects of prenatal intraamniotic surfactant or dexamethasone administration on lung development are comparable to changes induced by tracheal ligation in an animal model of congenital diaphragmatic hernia: Studies of lung glycogen content, elastic fiber density, and collagen content

Background/Purpose: A new noninvasive therapeutic strategy, which consisted of prenatal intraamniotic administration of porcine surfactant or dexameth asone, was previously used to prevent the functional and structural immatur ity of lungs associated with congenital diaphragmatic hernia (CDH), and its effects on lung development were comparable with the changes induced by tr acheal ligation (TL). The purpose of this study is to verify if this novel therapeutic modality has any effect in the elevated concentration of lung g lycogen and altered contents of lung elastic fiber and collagen promoted by CDH. Methods: A pilot study was performed to investigate in the rabbit model if the infused drugs in the amniotic cavity were aspirated by the CDH and non- CDH fetuses, and if there was correspondence between lung immaturity and hi gh glycogen concentration in lung tissue. Experimental groups consisted of 50 pregnant rabbits that underwent surgery on gestational day 24 or 25 to c reate left-sided diaphragmatic hernias in 56 fetuses, which were divided in groups according to the procedures: CDH (n = 12), CDH plus TL (n = 16), CD H plus intraamniotic administration of Curosurf (40 mg, n = 12), a nd CDH p lus intraamniotic administration of dexamethasone (n = 16). On gestational day 30, the fetuses were delivered by cesarean section, and 28 normal unope rated fetuses served as controls. The lungs were weighed and submitted to b iochemical determination of glycogen, morphometric evaluation of elastic fi bers, and colorimetric analysis of collagen. Results: in all CDH and non-CDH fetuses of the pilot study, the amniotic co ntent was massively aspirated into the lungs and trachea. There was an incr ease in lung glycogen content of fetuses at 24 days' gestation in compariso n with 20-day gestational age fetuses, followed by a decrease in the near f ull-term fetuses. in the fetuses of the experimental groups, CDH decreased the lung weight to body weight ratios of lungs ipsilateral to the hernia. T hese changes were reversed by TL but not by intraamniotic administration of surfactant or dexamethasone. Lung glycogen concentrations in the lungs of CDH fetuses were significantly higher than those in the control group. Thes e changes were reversed by intraamniotic administration of surfactant but n ot by dexamethasone administration or TL. in the lungs ipsilateral to the h ernia, surfactant administration promoted a significant decrease in glycoge n content to levels lower than control lungs. CDH promoted a decrease in th e linear density of elastic fibers in both lungs, ipsilateral and contralat eral to the hernia. This alteration was partially corrected by TL and surfa ctant administration, although dexamethasone administration had no effect. The concentrations of collagen in both lungs were increased significantly b y CDH, and these alterations could not be reversed by TL. In the lungs ipsi lateral to the hernia, intraamniotic administration of surfactant or dexame thasone promoted a significant decrease in the lung concentration of collag en but not to control levels. Conclusions: The positive effects of intraamniotic surfactant or dexamethas one administration on lung maturity of fetuses with CDH were observed. This therapy may be a substitute for TL. J Pediatr Surg 33:1776-1783. Copyright (C) 1998 by W.B. Saunders Company.