Am. J. Respir. Crit. Care Med., Volume 159, Number 3, March 1999, 917-923

Addition of ₁-Antitrypsin to Surfactant Improves Oxygenation in Surfactant-deficient Rats

YITZHAK BELAI, JOSÉ M. HERNÁNDEZ-JUVIEL, ROBERTA BRUNI, ALAN J. WARING, and FRANS J. WALTHER

Department of Pediatrics, Charles R. Drew University of Medicine and Science; and Perinatal Research Laboratories, Harbor-UCLA Research and Education Institute, University of California Los Angeles School of Medicine, Los Angeles, California

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 ₁-antitrypsin (₁-AT), an antiprotease, to surfactant improves its in vivo function. 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 ₁-AT per 75 mg PL. Adding ₁-AT did not affect in vitro surface activity, except for that of the PL mixture. Adult rats were ventilated with 100% O₂, 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 ₁-AT or 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 ₁-AT equalized oxygenation in all three 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 ₁-AT. These data suggest that the addition of ₁-AT to surfactant can exert a positive effect on oxygenation and surfactant metabolism in surfactant-deficient rats.