Nitrofen-Induced Diaphragmatic Hernias in Rats: Pulmonary Antioxidant Enzyme Activities

Abstract

ABSTRACT. We developed an experimental rat model of sive care and artificial ventilation (I). Mortality still remains at congenital diaphragmatic hernia (CDH) to elucidate the 50% as a result of pulmonary hypoplasia with or without peretiology and pathogenesis of this serious congenital anom-sistent pulmonary hypertension (2). Those infants with severe aly in humans and in particular to study the effects of a respiratory compromise need maximal ventilatory support and short period of artificial ventilation on the CDH lung in are often subjected to high inflation pressures and high percentrelation to antioxidant defense mechanisms. CDH was ages of oxygen. The side effects of respiratory treatment are well induced in about 60% of the offspring by maternal exposure known, (3) and the clinical picture of bronchopulmonary dysplato 2,4-dichlorophenyl-pnitrophenylether (Nitrofen) during sia has become one of the major sequelae of neonatal intensive pregnancy. This herbicide resembles thyroid hormone in care (4). Only a few reports describe defense mechanisms against chemical structure. The lungs of fetal rats (d 19, 20, 21, oxidative stress in the human neonatal lung (5). Most experiand 22) were examined for protein and DNA content and mental studies on the development of AOA have been done in activity of superoxide dismutase, catalase, and glutathione small rodents (6, 7). The effect of artificial ventilation on the peroxidase (GPX). The same parameters were assessed in lung has been studied only in larger animals such as the baboon tracheotomized newborn rats after pressure-controlled ar-(8). tificial ventilation with either room air or pure oxygen We described a model in which CDH was induced in fetal during a short period of 5 h. In both CDH rats and controls, Sprague-Dawley rats by maternal exposure to a single dose of wet lung weight increased during gestation. At term, CDH 2,4-dichlorophenyl-pnitrophenylether (Nitrofen, Wako Chemirats had significantly lower mean lung weights than con-cals, Neuss, Germany) during pregnancy (9, 10). The incidence trols. Neither group differed in protein and DNA content of CDH in the treatment group was up to 60%. The diaphragper mg lung or superoxide dismutase, catalase, and GPX matic defect was mainly right-sided with severe hypoplasia of the activity before and at birth. After artificial ventilation of lung as reflected by decreased lung weight/body weight ratios. neonates with air and pure oxygen, superoxide dismutase No correlation was found between the size of the defect and the activity tended to decrease, whereas catalase activity re-ipsilateral and contralateral lung weights (9). Without artificial mained virtually unchanged in the CDH lung. However, ventilation, more than 80% of the CDH animals died within 2 GPX activity in the CDH lung was reduced to 80% of h after birth as a result of severe respiratory insufficiency. initial activity at term after ventilation with air and to 70%In the present study, we report 1 )

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

“…The results of fetal lung morphology and are in agreement with previous studies that observed fetuses of progressively smaller size when exposed to nitrofen (N-) and with CDH, pulmonary hypoplasia in both being higher in CDH than in C fetuses 14,29,30 . Ventilation for a short time did not significantly alter this pattern.…”

“…The adaptation for ventilation in fetal rats was described in 1992 14 . However, this model was reproduced in only three other studies [15][16][17] .…”

“…Several models of ventilation in larger animals have been described in CDH, such as in sheep [11][12][13] and rabbits 14,15 , but these species lack options for conducting molecular studies. Due to the difficulty of lung ventilation in these patients, only one model has been described in small animals.…”

Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model

“…We administered a single 100-mg dose of nitrofen at E9 and confirmed the diaphragm defects in 48% of the rat pups. This rate is acceptable as compared with those in other reports (19,20).…”

Expression Patterns of Heat Shock Proteins in Lungs of Neonates With Congenital Diaphragmatic Hernia

“…7,8,20,22 Possibly, the enhanced expression of HSPs in the CDH group reflects a neonatal attempt to establish a protective mechanism against stress, as shown earlier for antioxidant enzyme activity in a rat CDH model. 23 It has been well documented that the small-diameter pulmonary arteries are the most important vessels in the regulation of pulmonary blood flow and pressure. 2,3,19 Structural changes have been described in pulmonary arteries of patients with CDH complicated by PH.…”