Pulmonary hypertension produced in rats by ingestion of Crotalaria spectabilis seeds.

Young rats fed on a diet which contains Crotalaria spectabilis seeds or the pyrrolizidine alkaloid monocrotaline die from congestive heart failure within 36 to 60 days. At necropsy they are found to have ascites, pleural effusions, and cardiac enlargement due to right ventricular hypertrophy (Turner and Lalich, 1965; Kay and Heath, 1966). Microscopic examination reveals an increase in the medial thickness of the pulmonary trunk (Heath and Kay, 1967) and small pulmonary arteries (Turner and Lalich, 1965 ; Kay and Heath, 1966), and in about one-third of the animals an acute necrotizing pulmonary arteritis (Lalich and Merkow, 1961; Kay and Heath, 1966). Since similar changes in the heart weight and pulmonary vasculature in man are well known to be associated with severe pulmonary hypertension (Wagenvoort, Heath, and Edwards, 1964) we thought it likely that the pulmonary vascular lesions produced in rats by Crotalaria spectabilis seeds are also associated with an elevation of the pulmonary artery pressure. It has never been shown that the oral administration of any agent can produce pulmonary hypertension, so we considered that its direct demonstration in rats fed with such seeds would be of considerable significance. Accordingly we measured right atrial and ventricular pressures in a group of rats maintained on a diet containing Cratalaria spectabilis seeds and compared these with values obtained from a group of control rats. In addition, we investigated the relation between right ventricular systolic pressure on the one hand, and the medial thickness of the small pulmonary arteries and the pulmonary trunk and the right ven-tricular weight on the other. METHODS