Pulmonary toxicity of monocrotaline differs at critical periods of lung development.
We injected 3-day-old (neonatal), 8-day-old (infant), and 8-wk-old (adult) Sprague-Dawley rats with monocrotaline to examine the effect of a toxic agent at various stages of lung development. Two and four weeks after injection the rats were killed and the heart and lungs removed: the right and left ventricles were separated and weighed, the pulmonary artery was injected with barium-gelatin, and the lung was fixed in the inflated state. Morphometric techniques were applied to assess lung volume, alveolar size and number, and arterial size, muscularity, and concentration relative to alveolar. Rats injected with monocrotaline in the neonatal period did not survive to 3 wk. After 2 wk, there was no significant right ventricular hypertrophy and pulmonary vascular changes were no worse than in the other rat groups injected with monocrotaline, but alveolar development was severely impaired; less than one-third the normal number was present. Rats injected with monocrotaline in infancy had normal alveolar development. After 2-wk, the arterial changes, i.e. extension of muscle into peripheral arteries, medial hypertrophy of muscular arteries, and decreased arterial concentration relative to alveolar were similar to those observed in adult rats. After 4 wk, there was a decrease in medial hypertrophy associated with growth in artery size and only a lack of regression of right ventricular weight. In adult rats, after 4 wk medial hypertrophy became progressively more severe, the arterial concentration relative to alveolar decreased further, and right ventricular hypertrophy developed.(ABSTRACT TRUNCATED AT 250 WORDS)
Todd
L
L
Mullen
M
M
Olley
P M
PM
Rabinovitch
M
M
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced; D005260:Female; D005544:Forecasting; D008168:Lung / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D016686:Monocrotaline; D011652:Pulmonary Circulation / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline