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Am J Physiol Lung Cell Mol Physiol 277: L423-L429, 1999;
1040-0605/99 $5.00
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Vol. 277, Issue 2, L423-L429, August 1999

RAPID COMMUNICATION
Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats

Bernard Thébaud1,2, Dick Tibboel3, Caroline Rambaud4, Jean-Christophe Mercier5, Jacques R. Bourbon6, A. Tuan Dinh-Xuan2, and Stephen L. Archer7

1 Réanimation Néonatale and 4 Service d'Anatomo-Pathologie, Hôpital Antoine Béclère, 92141 Clamart; 2 Service de Physiologie, Hôpital Cochin, Université René Descartes, 75679 Paris Cedex 14; 5 Réanimation Pédiatrique, Hôpital Robert Debré, 75019 Paris; 6 Institut National de la Sante et de la Recherche Médicale Unité 319, Université Paris 7, 75251 Paris, France; 3 Pediatric Surgery, Sophia Children's Hospital, 3015 Rotterdam, The Netherlands; and 7 Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2B7

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12 of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before (day 10), concomitant with (day 12), or after (day 14) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A (day 10, 44%; day 12, 20%; and day 14, 40%) compared with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups (day 10, 40%; day 12, 58%; and day 14, 70%) compared with the nitrofen-treated group (16%; P < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation.

lung hypoplasia; lung development; retinoic acid; persistent pulmonary hypertension of the newborn; pulmonary circulation


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