Pathophysiology of Dehydromonocrotaline-Induced Pulmonary Fibrosis in the Beagle

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Abstract
The sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline were characterized in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascular resistance of the experimental animals were significantly greater than the controls (P < 0.01). Right ventricular work increased from a baseline mean of 0.58-1.40 kg .cntdot. 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 mechanisms by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification, although the fraction of air space is apparently 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.