Inhaled nitric oxide increases survival rates in newborn rats with congenital diaphragmatic hernia

The high mortality of newborn infants with congenital diaphragmatic hernia (CDH) can be partly attributed to pulmonary hypertension causing extrapulmonary right-to-left shunting with subsequent severe hypoxemia. Inhaled nitric oxide (NO) may reduce elevated pulmonary artery pressure and has been successfully improve arterial oxygenation in some newborns with CDH. However, it is not clear whether inhaled NO will actually improve survival of newborns with CDH. We therefore investigated the effect of inhaled NO on the survival rate of newborn rats with CDH following intrauterine exposure to nitrofen. A total of 151 newborn rats (9 litters) were exposed to nitrofen on day 11 of pregnancy, After spontaneous delivery, 63 newborn rats (4 litters) were allowed to spontaneously breathe air containing NO (80 parts per million), while 88 newborn rats (5 litters) were given air without NO. Survival was checked 15 min after birth and then hourly until the animals were sacrificed at 24 h of age to verify the absence or presence of CDH. The 2 groups of newborn rats breathing air with or without NO did not differ significantly with respect to the presence or size of CDH. Twenty-four of 63 (38%) newborn rats breathing air with NO survived for 24 h, compared to 12 of 88 (14%) rats breathing air alone (p < 0.01). Of newborn rats that were actually found to have CDH (n = 113), 8 of 42 (19%) animals breathing air with NO survived for 24 h, compared to 2 of 71 (2.8%) animals breathing air alone (p < 0.01). In animals with CDH confirmed by autopsy, the median survival time was significantly longer with NO (p < 0.001) ( 2 h, interquartile range 2h-15h), than those breathing or without NO (median/interquartile range 15 min). We conclude that in the nitrofen rat CDH model, significantly improved survival rates occur with inhaled NO as a sole intervention. The combined impact of inhaled NO and mechanical ventilation remains to be determined.