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 protect neonatal rats from the pulmonary parenchymal and vascular effects resulting from hyperoxic exposure. Neonatal rats born into and maintained in hyperoxia (60% fraction of inspired oxygen) or room air were injected 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 end of the experimental period, we measured body weight, lung compliance, lung volume, alveoli per mm2, and total number of alveoli and assessed right ventricular hypertrophy and vascular changes consisting of medial hypertrophy, muscular extension into peripheral, normally nonmuscular 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 vascular changes of medial hypertrophy of muscular arteries and muscularization of distal arteries. Reduced lung compliance in the hyperoxic but alpha 1-AT-untreated rats was associated with a reduction in lung elastin compared with room-air or alpha 1-AT-treated rats. In room-air rats, alpha 1-AT treatment increased lung compliance but also reduced the number of arteries relative to the number of alveoli, a feature that was not, however, associated with right ventricular hypertrophy. Our data suggest that supplemental alpha 1-AT might restore the imbalance in elastolytic activity induced by hyperoxia and thereby alleviate the toxic effects on lung parenchymal and vascular development.
Koppel
R
R
Division of Cardiovascular, Hospital for Sick Children, Toronto, Canada.
Han
R N
RN
Cox
D
D
Tanswell
A K
AK
Rabinovitch
M
M
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000187:drug effects; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D000515:alpha 1-Antitrypsin; D010100:Oxygen