ALPHA(1)-ANTITRYPSIN PROTECTS NEONATAL RATS FROM PULMONARY VASCULAR AND PARENCHYMAL EFFECTS OF OXYGEN-TOXICITY

We investigated whether alpha(1)-antitrypsin (alpha(1)-AT) might prote ct neonatal rats from the pulmonary parenchymal and vascular effects r esulting from hyperoxic exposure. Neonatal rats born into and maintain ed in hyperoxia (60% fraction of inspired oxygen) or room air were inj ected with a loading dose of alpha(1)-AT (72 mg/kg) followed by 36 mg/ kg every 72 h or with vehicle during the first 14 d of life. At the en d of the experimental period, we measured body weight, lung compliance , lung volume, alveoli per mm(2), and total number of alveoli and asse ssed right ventricular hypertrophy and vascular changes consisting of medial hypertrophy, muscular extension into peripheral, normally nonmu scular arteries, and number of peripheral arteries relative to alveoli . Our data show that alpha(1)-AT treatment prevented the reduced lung compliance observed in the untreated hyperoxia-exposed neonatal rats, as well as the right ventricular hypertrophy and the associated vascul ar changes of medial hypertrophy of muscular arteries and muscularizat ion of distal arteries. Reduced lung compliance in the hyperoxic but a lpha(1)-AT-untreated rats was associated with a reduction in lung elas tin compared with room-air or alpha(1)-AT-treated rats. In room-air ra ts, alpha(1)-AT treatment increased lung compliance but also reduced t he number of arteries relative to the number of alveoli, a feature tha t was not, however, associated with right ventricular hypertrophy. Our data suggest that supplemental alpha(1)-AT might restore the imbalanc e in elastolytic activity induced by hyperoxia and thereby alleviate t he toxic effects on lung parenchymal and vascular development.