EFFECTS OF THE NA-VENTRICULAR FUNCTION OF POSTISCHEMIC HEARTS( ANTAGONIST CIBENZOLINE ON LEFT)

The negative inotropic effect of antiarrhythmic drugs is a major drawb ack in antiarrhythmic drug therapy, especially in patients with reduce d contractile function of the left ventricle. The circulatory and myoc ardial effects of the new class I antiarrhythmic drug (a Na+ antagonis t), cibenzoline (2 mg/kg i.v.), were investigated in 47 open-chest rat s with normal and postischemic myocardium (3 x 4 minutes of global isc hemia). Hemodynamic measurements in the intact circulation and isovolu mic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dt(max)) were compared to saline controls. In r ats with postischemic myocardium, cibenzoline caused a significant (p < 0.001) decrease in the cardiac output for 38%, in the dP/dt(max) for 30%, and in the peak isovolumic dP/dt(max) for 19% at the end of infu sion (compared to the control). The heart rate was reduced by 22% (p < 0.001), the mean aortic pressure by 22% (p < 0.001), and the calculat ed systemic resistance by 20% (p < 0.001). In contrast to the results with postischemic myocardium, no important changes in the hemodynamics were detectable after an identical dose in normal animals without lef t ventricular dysfunction. The results indicate that standard doses of the Naf antagonist cibenzoline may induce significant cardiodepressan t effects on postischemic left ventricles with reduced function.