Addition of alpha(1)-antitrypsin to surfactant improves oxygenation in surfactant-deficient rats

During its life cycle, surfactant converts from highly surface active, larg e aggregates to less surface active, smaller aggregates. This process is pr obably regulated by a serine protease. We tested whether adding alpha(1)-an titrypsin (alpha(1)-AT), an antiprotease, to surfactant improves its in viv o function. alpha(1)-AT was added to Survanta, to a standard phospholipid ( PL) mixture, and to a synthetic surfactant (BC mixture = PL mixture + synth etic 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 fo r that of the Pt mixture. Adult rats were ventilated with 100% O-2, at a ti dal 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, pre ssure-volume curves were generated, and the rats' lungs were relavaged. Sur factant treatment improved oxygenation in the order: BC mixture > Survanta > PL mixture. Addition of alpha(1)-AT equalized oxygenation in all three al pha(1)-AT groups, but decreased respiratory system compliance in the groups given Survanta and PL mixture. Particle sizing of the final lung lavages s howed preservation of large surfactant aggregates after treatment with alph a(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 sur factant-deficient rats.