Fulvine and the pulmonary circulation

Abstract

The pyrrolizidine alkaloid, fulvine, is now accepted as a major cause of veno-occlusive disease of the liver in the West Indies, where it is ingested as a decoction of the plant Crotalaria fulva in bush tea. Fulvine is similar in chemical structure to monocrotaline, which is known to cause pulmonary hypertension in rats. Thirty young female rats were given a single dose of fulvine either by intraperitoneal injection (50 mg/kg body weight) or by stomach tube (80 mg/kg body weight). Eleven of these rats died of acute haemorrhagic centrilobular necrosis of the liver, and two of pneumonia, within 23 days of receiving fulvine. These 13 showed no evidence of hypertensive pulmonary vascular disease. The remaining 17 rats (which survived from 24 to 37 days) developed hypertensive pulmonary vascular disease with right ventricular hypertrophy together with medial thickening of the pulmonary trunk and muscular pulmonary arteries. The pulmonary arterioles showed hypertensive changes and some contained thrombi. In four animals an acute necrotizing arteritis also occurred. We have shown that fulvine resembles monocrotaline in its ability to produce pulmonary hypertension in rats. We suggest that, in any patient presenting with unexplained pulmonary hypertension, a careful enquiry should be made to elicit the possibility of recent ingestion of drugs or plant extracts that may have caused a rise in the pulmonary arterial pressure.