Addition of alpha1-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 alpha1-antitrypsin (alpha1-AT), an antiprotease, to surfactant improves its in vivo function. alpha1-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 alpha1-AT per 75 mg PL. Adding alpha1-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 PaO2 dropped below 100 mm Hg, at which time 100 mg/kg of surfactant with or without alpha1-AT or alpha1-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 alpha1-AT equalized oxygenation in all three alpha1-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 alpha1-AT. These data suggest that the addition of alpha1-AT to surfactant can exert a positive effect on oxygenation and surfactant metabolism in surfactant-deficient rats.
Belai
Y
Y
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Perinatal Research Laboratories, Harbor-UCLA Research and Education Institute, University of California Los Angeles School of Medicine, Los Angeles, USA.
Hernández-Juviel
J M
JM
Bruni
R
R
Waring
A J
AJ
Walther
F J
FJ
D000818:Animals; D001688:Biological Products; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008170:Lung Compliance; D008297:Male; D010100:Oxygen / Q000502:physiology*; D010316:Particle Size; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007507:Therapeutic Irrigation; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000494:pharmacology*
D001688:Biological Products; D011663:Pulmonary Surfactants; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C072197:beractant; D010100:Oxygen