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.
OBJECTIVE
A new noninvasive therapeutic strategy, which consisted of prenatal intraamniotic administration of porcine surfactant or dexamethasone, was previously used to prevent the functional and structural immaturity of lungs associated with congenital diaphragmatic hernia (CDH), and its effects on lung development were comparable with the changes induced by tracheal ligation (TL). The purpose of this study is to verify if this novel therapeutic modality has any effect in the elevated concentration of lung glycogen 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 high glycogen concentration in lung tissue. Experimental groups consisted of 50 pregnant rabbits that underwent surgery on gestational day 24 or 25 to create left-sided diaphragmatic hernias in 56 fetuses, which were divided in groups according to the procedures: CDH (n = 12), CDH plus TL (n = 16), CDH plus intraamniotic administration of Curosurf (40 mg, n = 12), and CDH plus intraamniotic administration of dexamethasone (n = 16). On gestational day 30, the fetuses were delivered by cesarean section, and 28 normal unoperated fetuses served as controls. The lungs were weighed and submitted to biochemical determination of glycogen, morphometric evaluation of elastic fibers, and colorimetric analysis of collagen.


RESULTS
In all CDH and non-CDH fetuses of the pilot study, the amniotic content was massively aspirated into the lungs and trachea. There was an increase in lung glycogen content of fetuses at 24 days' gestation in comparison with 20-day gestational age fetuses, followed by a decrease in the near full-term fetuses. In the fetuses of the experimental groups, CDH decreased the lung weight to body weight ratios of lungs ipsilateral to the hernia. These 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. These changes were reversed by intraamniotic administration of surfactant but not by dexamethasone administration or TL. In the lungs ipsilateral to the hernia, surfactant administration promoted a significant decrease in glycogen content to levels lower than control lungs. CDH promoted a decrease in the linear density of elastic fibers in both lungs, ipsilateral and contralateral to the hernia. This alteration was partially corrected by TL and surfactant administration, although dexamethasone administration had no effect. The concentrations of collagen in both lungs were increased significantly by CDH, and these alterations could not be reversed by TL. In the lungs ipsilateral to the hernia, intraamniotic administration of surfactant or dexamethasone promoted a significant decrease in the lung concentration of collagen but not to control levels.


CONCLUSIONS
The positive effects of intraamniotic surfactant or dexamethasone administration on lung maturity of fetuses with CDH were observed. This therapy may be a substitute for TL.
Tannuri
U
U
Pediatric Surgery Laboratory Division, University of São Paulo Medical School, Brazil.
Rodrigues
C J
CJ
Maksoud-Filho
J G
JG
Santos
M M
MM
Tannuri
A C
AC
Rodrigues
A J
AJ
D000818:Animals; D003094:Collagen / Q000032:analysis; D003124:Colorimetry; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004547:Elastic Tissue; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D006003:Glycogen / Q000032:analysis; D006548:Hernia, Diaphragmatic / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008026:Ligation; D008168:Lung / Q000737:chemistry / Q000196:embryology*; D010865:Pilot Projects; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000187:drug effects*; D011817:Rabbits; D014132:Trachea / Q000601:surgery
D011663:Pulmonary Surfactants; D003907:Dexamethasone; D006003:Glycogen; D003094:Collagen