PATHOPHYSIOLOGY OF CONGENITAL DIAPHRAGMATIC-HERNIA .8. INHALED NITRIC-OXIDE REQUIRES EXOGENOUS SURFACTANT THERAPY IN THE LAMB MODEL OF CONGENITAL DIAPHRAGMATIC-HERNIA

The pathophysiology of the lamb model of congenital diaphragmatic hern ia (CDH) involves pulmonary hypoplasia, pulmonary hypertension, and su rfactant deficiency. Inhaled nitric oxide (NO) is a highly selective p ulmonary vasodilator. The aim of this study was to determine the effec ts of inhaled NO on pulmonary gas exchange, acid-base balance, and pul monary pressures in a lamb model of CDH with or without exogenous surf actant therapy. At the gestational age of 78 days (full term, 145 days ) 11 lamb fetuses had a diaphragmatic hernia created via a left thorac otomy and then were allowed to continue development in utero. After ce sarean section, performed at term, six lambs received exogenous surfac tant therapy (50 mg/kg, Infasurf) and five served as controls. All ani mals were pressure-ventilated for 30 minutes and then received 80 ppm of inhaled NO at an F1O2 of .9 for a 10-minute interval. Compared with the control lambs, the lambs with exogenous surfactant therapy had hi gher pH (7.17 +/- .06 v 6.96 +/- .07; P < .05), lower PCO2 (73 +/- 8 v 122 +/- 20, p < .05), and higher PO2 (153 +/- 38 v 50 +/- 23; P < .05 ). In control CDH lambs (without surfactant), inhaled NO did not impro ve pH, PCO2, Or PO2, or decrease pulmonary artery pressure. In CDH lam bs given exogenous surfactant, NO decreased pulmonary artery pressures (42 +/- 4 v 53 +/- 5; P < .005) and further improved PCO2 and PO2. NO also made the difference between pulmonary and systemic artery pressu res more negative in the surfactant-treated lambs (-15 +/- 4 v -2.3 +/ - 2.4; P < .005). These data suggest that inhaled NO only improves oxy genation and decreases pulmonary artery pressure when the lamb model i s given exogenous surfactant therapy. These results support our earlie r finding that surfactant deficiency and/or inactivation is important in the pathophysiology of CDH. To our knowledge, this is the first rep ort of the efficacy of inhaled NO after exogenous surfactant therapy. Copyright (C) 1995 by W.B. Saunders Company