Cardiotoxicity of high doses of isoproterenol on cardiac haemodynamics and metabolism in SHR and WKY rats

The haemodynamic and metabolic effects on the heart due to high doses of isoproterenol were compared in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. In baseline conditions, the hypertrophied SHR heart displayed perfectly constant haemodynamics but had fewer energy reserves than the WKY heart. Isoproterenol (2 X 25 mg/kg, s.c.) caused high mortality, myocardial ischaemia, and heart failure in the SHR. These effects were accompanied by anaerobic metabolism. In the WKY rats, on the other hand, isoproterenol caused no changes in ST-segment elevation and no cardiac insufficiency; in addition, aerobic metabolism was maintained. A marked drop in coronary perfusion pressure and excessive accumulation of calcium in the myocardium account, in part, for the effects seen in the SHR. The results indicate that isoproterenol-induced heart failure in the SHR might be a useful model for selecting compounds designed to treat this disease.