Pathophysiology of dehydromonocrotaline-induced pulmonary fibrosis in the beagle.
The purpose of this study was to characterize the sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascualr resistance of the experimental animals were significantly greater than the controls (p less than 0.01). Right ventricular work increased from a baseline mean of 0.58 to 1.40 kg . m/min. Morphological and morphometrical analyses revealed alveolar edema, increased numbers of alveolar macrophages, cellular hyperplasia in the alveolar septa, and a progressive interstitial fibrosis. The precise mechansims by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification; however, our data indicate that the fraction of air space is reduced relative to the fraction of tissue space, and this change occurs with concurrent fibrosis in the alveolar septa and an increased pulmonary arterial pressure although hypoxia was not clinically detectable.
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D008297:Male; D010100:Oxygen / Q000097:blood; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000503:physiopathology*; D011763:Pyrrolizidine Alkaloids; D014655:Vascular Resistance / Q000187:drug effects
D011763:Pyrrolizidine Alkaloids; D002245:Carbon Dioxide; D010100:Oxygen