Addition of α1-antitrypsin to surfactant improves oxygenation in surfactant-deficient rats

During its life cycle, surfactant converts from highly surface active, large aggregates to less surface active, smaller aggregates. This process is probably regulated by a serine protease. We tested whether adding alpha(1)-antitrypsin (alpha(1)-AT), an antiprotease, to surfactant improves its in vivo function. alpha(1)-AT was added to Survanta, to a standard phospholipid (PL) mixture, and to a synthetic surfactant (BC mixture = PL mixture + synthetic surfactant proteins B and C) at a dose of 100 mg alpha(1)-AT per 75 mg FL. Adding alpha(1)-AT did not affect in vitro surface activity, except for that of the Pt mixture. Adult rats were ventilated with 100% O-2, at a tidal volume of 7.5 ml/kg and a ventilatory rate of 60 breaths/min. The rats' lungs were lavaged with saline until the Pa-o2 dropped below 100 mm Hg, at which time 100 mg/kg of surfactant with or without alpha(1)-AT or alpha(1)-AT alone was instilled. After 1 h of ventilation the rats were killed, pressure-volume curves were generated, and the rats' lungs were relavaged. Surfactant treatment improved oxygenation in the order: BC mixture > Survanta > PL mixture. Addition of alpha(1)-AT equalized oxygenation in all three alpha(1)-AT groups, but decreased respiratory system compliance in the groups given Survanta and PL mixture. Particle sizing of the final lung lavages showed preservation of large surfactant aggregates after treatment with alpha(1)-AT. These data suggest that the addition of alpha(1)-AT to surfactant can exert a positive effect on oxygenation and surfactant metabolism in surfactant-deficient rats.