Pulmonary mechanical, ventilatory, and gas exchange abnormalities in rats with monocrotaline-induced pulmonary...

Recent clinical studies have suggested that peripheral airways dysfunction contributes to the pathogenesis of idiopathic pulmonary hypertension. To determine whether similar peripheral airways defects occur in a common animal model of pulmonary hypertension, pulmonary function tests were performed in adult male rats rendered pulmonary hypertensive with a single subcutaneous injection of monocrotaline. At 20 days post treatment, animals exhibited well-developed right ventricular hypertrophy coincident with significant changes in lung volumes, pulmonary mechanics, and gas exchange function indicative of a severe combined restrictive and obstructive airways disorder. Morphologic changes in alveolar integrity compatible with such a pulmonary defect also were observed in monocrotaline-treated animals. The specific changes in pulmonary function observed in monocrotaline-treated rats were qualitatively similar to abnormalities reported in patients with idiopathic pulmonary hypertension. These results demonstrate that significant pulmonary mechanical, ventilatory, and gas exchange dysfunction is present in rats with monocrotaline-induced pulmonary hypertension and highlight the suitability of this model for investigating a potential contributory role of pulmonary function abnormalities in the pathogenesis of this disorder.