COMBINED EFFECTS OF NITRIC-OXIDE AND HYPEROXIA ON SURFACTANT FUNCTIONAND PULMONARY INFLAMMATION

NO and its derivative ONOO- are potent free radicals that can cause ce ll damage, especially in the presence of O-2. To determine the potenti al pulmonary toxicities of nitric oxide (NO) and peroxynitrite (ONOO-) in vitro, Survanta (2.5 mg/ml) was exposed to ONOO- (0.3-8 mM) in the presence of two different buffering systems (N-2-hydroxyethylpiperazi ne-N'-2-ethanesulfonic acid and phosphate buffer) and minimum surface tension (MST) was determined with an oscillating bubble surfactometer. Significant increases in MST were seen only with exposure to 8 mM ONO O-, indicating that in vitro, high concentrations of ONOO- can inhibit natural surfactant function. The in vivo effects of NO and hyperoxia were then studied in four groups of newborn piglets ventilated for 48 h with 21% O-2, 100% O-2, 21% O-2 and 100 ppm NO, or with 90% O-2 and 100 ppm NO. Five animals served as an untreated control group. Broncho alveolar lavage fluid (BAL) obtained at 48 h was subjected to centrifu gation and the surfactant pellet was reconstituted to 5 mg phospholipi d/ml. Significant increases in MST were seen in surfactant from piglet s ventilated with NO and 90% O-2, compared with either untreated contr ols or piglets ventilated with 21% O-2 for 48 h (P < 0.05, analysis of variance). Significant increases in neutrophil chemotactic activity ( NCA) of BAL were also found in the NO and O-2 group (P < 0.05), with s ignificant positive interaction between NO and O-2 found (P < 0.01). T hese data indicate that inhaled NO, in vivo, in the presence of hypero xia, causes significant surfactant dysfunction and early evidence of p ulmonary inflammation. This suggests that NO therapy may exacerbate pu lmonary O-2 toxicity.