Effects of disopyramide on the electrocardiogram and ventricular function in the unanesthetized dog

The antiarrhythmic compound disopyramide has been shown to possess negative inotropic effects. The present study was conducted to establish the effects of graded doses of disopyramide on ventricular function and electrocardiograms from healthy, awake dogs. Electrocardiograms and echocardiograms were obtained during a control period, and during an experimental period in which the six dogs on test received 7.5, 15 or 30 mg disopyramide per kg body weight orally three times per day. Six other dogs served as vehicle controls. No changes of statistical significance occurred in heart rate. The PQ interval was prolonged at all doses, the QRS complex was prolonged only at the highest dose, and the QT interval was prolonged at the intermediate and high doses. Left ventricular pre-ejection period (PEP) was prolonged in a dose-dependent relationship, and the left ventricular ejection time (ET) was shortened only at the highest dose. The percent shortening fraction of the left ventricle (% delta D) decreased significantly at intermediate and high doses, while the ratio of pre-ejection period to ejection time increased in a dose-dependent relationship. Conclusions are that even in therapeutic levels disopyramide produces significant reduction in left ventricular function, and that ratio of PEP/ET correlates better with the dose of disopyramide than did % delta D. This study demonstrates the feasibility of evaluating cardiac effects of compounds by non-invasive means.