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 a1-antitrypsin (α1-AT), an antiprotease, to surfactant improves its in vivo function. α1-AT was added to Survanta® and a synthetic surfactant (BC: phospholipids with 3% surfactant peptide B1-78 and 1% palmitoylated surfactant peptide C1-35) at a dose of 100 mg/3 ml surfactant. Adding α1-AT to Survanta and BC did not affect surface activity on a Langmuir/Wilhelmy balance. Adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 ml/kg, and a rate of 60/min. Their lungs were lavaged with saline until the PaO2 dropped below 80 torr, at which time 100 mg/kg of surfactant was instilled. After 60 min of ventilation, the rats were killed and their lungs lavaged. Survanta increased mean arterial/Alveolar PO2 ratios by 91% over post-lavage values versus 136% for Survanta plus α1-AT (p<0.001). BC increased mean arterial/Alveolar PO2 ratios by 173% versus 218% for BC plus α1-AT (p=0.002). Phospholipids in the first and final lavages of rats treated with surfactant without α1-AT were equal, but reduced in the final lavages of rats treated with surfactants plusα1-AT. Total proteins in the final lavages of all groups (1764± 345 μg/ml) were higher (p<0.001) than in the first lavages (211± 59 μg/ml). These data suggest that the addition ofα1-antitrypsin to surfactant has a positive effect on oxygenation in surfactant-deficient rats.
