HYPOXIC PULMONARY VASOCONSTRICTION IS IMPAIRED IN RATS WITH NITROFEN-INDUCED CONGENITAL DIAPHRAGMATIC-HERNIA

Background: Pulmonary hypertension and persistent fetal circulation co ntribute to the high mortality rate associated with congenital diaphra gmatic hernia (CDH). Morphological alterations of the pulmonary vascul ature in infants with CDH are thought to contribute to exaggerated vas oconstrictor responses to normal vasoconstrictor stimuli. In the pulmo nary circulation, hypoxia is a potent vasoconstrictor. Under pathologi cal conditions, hypoxia-induced vasoconstriction may contribute to the development of pulmonary hypertension. Methods: The authors have used the nitrofen-induced model of congenital diaphragmatic hernia in rats to investigate the magnitude of the hypoxic vasoconstrictor response. Congenital diaphragmatic hernias were induced in fetal rats by feedin g nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) to pregnant Spragu e-Dawley rats at midgestation. Hypoxia-induced vasoconstriction was me asured in isolated, perfused third-generation pulmonary arterioles fro m normal rats and from rats with nitrofen-induced CDH. Results: The hy poxic vasoconstrictor response was significantly blunted in the pulmon ary arterioles of fetal rats with nitrofen-induced (2%+/-1% vasoconstr iction), as compared with the responses observed in normal fetal rats (15% +/- 3% vasoconstriction, P=.004). Conclusion: Blunting of the hyp oxic pulmonary vasoconstrictor response may contribute to ventilation- perfusion mismatching in infants with CDH. Copyright (C) 1998 by W.B. Saunders Company.