INHALED NITRIC OXIDE (I-NO) DELAYS THE HYPEROXIA-INDUCED CONVERSION OF LARGE SURFACTANT AGGREGATES TO SMALL VESICLES IN PRETERM RABBITS. † 1291

I-NO decreases the high pulmonary vascular resistance at birth, and may affect other structures in the lung, particularly the lining of the airspaces. NO has been shown to act variably as a pro- and antioxidant in vitro. The aim of the present study was to investigate whether I-NO alters the surfactant in the epithelial lining fluid of premature rabbits during oxidant stress. Preterm rabbits (gestation 29 d, term 31 d) were nose-only exposed to NO (14 ppm) and 95% O₂ for 20 hrs. The controls were exposed to either 95% O₂ or to room air. The animals received intragastric formula, and the breathing zone was monitored for NO and NO₂. After the exposure, bronchoalveolar lavage (BAL) was performed and the large surfactant aggregate fraction isolated. The total phosphatidylcholine (PC) in BAL and in the large aggregate surfactant fraction were measured. Surfactant protein B(SP-B) was quantitated using ELISA, and SP-A by Western blot. The cellular fraction of BAL was analyzed for differential cell count, and respiratory burst activity; the acellular fraction of BAL for nitrotyrosine and malondialdehyde. Altogether 144 animals were studied. There was no difference in mortality between the groups. The cellular fraction of BAL revealed no differences between the groups. I-NO was not associated with increased nitrotyrosine or malondialdehyde in BAL. There was no difference in PC or saturated PC content in BAL. The concentrations of SP-B and the amount of large aggregates (% of total PC in BAL) were as follows:Table Exposure to O₂ decreased the distribution of large surfactant aggregates. I-NO delayed the conversion of large to small surfactant aggregates that are not surface active and that are deficient in surfactant proteins. Inhaled NO tended to increase SP-B and SP-A in BAL. According to present results oxidant stress increases the conversion of large surfactant aggregates to small vesicles in the premature. The present data suggests I-NO at a low dose maintains the surface activity in the epithelial lining of the airspaces.

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