Effects of ergometrine (ergonovine) on the isolated atherosclerotic heart of the cholsterol-fed rabbit.

Ergometrine usually depresses the S-T segment as in coronary insufficiency, when injected intravenously in rabbits with experimental coronary atherosclerosis and in patients with effort angina, but not in normal animals and man. To explain this difference, we carried out Langendorff perfusion studies in 32 normal and 29 atherosclerotic isolated rabbit hearts. Preliminary tests with ergometrine were done to ensure that advanced coronary atherosclerosis had developed in the rabbits fed a cholesterol diet; pathological examination of the heart after perfusion confirmed the result of the final test with ergometrine. Before drugs were perfused, the basal rate of coronary flow was greater, the heart rate was slower and the contractile amplitude was smaller in the atherosclerotic than in the normal hearts; nitroglycerin markedly increased flow in both normal and atherosclerotic groups. Ergometrine consistently caused a reduction in contractile amplitude with negligible changes in heart rate in both normal and atherosclerotic hearts. On coronary flow, however, the effects of ergometrine differed significantly in these groups; in doses of between 0.2 and 0.4 mg., the average decrease in flow was 8% in normal and 22% in atherosclerotic hearts. The effect was more variable in normal hearts and an increase in flow sometimes occurred. The difference in the response of normal and atherosclerotic hearts was particularly striking when ergometrine was given during recovery from a reduction of coronary flow which had been induced by vasopressin. Ergometrine then uniformly increased flow in the normal, but usually had the opposite effect in the atherosclerotic heart. In normal and atherosclerotic hearts, cardiac effects of vasopressin were similar. Tachyphylaxis to vasopressin, but not to ergometrine, was observed.