Negative inotropic effect of class-I-antiarrhythmic drugs: Comparison of flecainide with disopyramide and quinidine

An important side-effect of antiarrhythmic drugs is their negative inotropic action. To investigate this after i.v. administration we compared the newer class-I-antiarrhythmic drug flecainide (2mg, 4 mg and 8 mg kg-1) with disopyramide (1 mg, 4 mg and 8 mg kg-1), quinidine (5mg and 10 mg kg-1) and saline (controls). Isovolumic measurements of ventricular function by short aortic crossclamping were performed in 82 openchest rats and peak left ventricular isovolumic pressure (LVSP) and peak isovolumic dp/dt max were determined 5 and 15 minutes after intravenous drug injection. All drugs decreased isovolumic indices of myocardial function dose-dependently. Flecainide reduced peak isovolumic LVSP and dp/dt max only after 8 mg kg-1 (to 85±3% and 45±5%, resp., means±SE, P<0.01), 2mg kg-1 and 4 mg kg-1 had no significant effect. Disopyramide influenced myocardial function already at 4 mg kg -1 (peak LVSP 88±4%, P<0.05, peak dp/dt max 64±7%, P<0.01, means±SE), 8 mg kg-1 had an even more marked depressive effect (peak LVSP 81±4%, peak dp/dt max 50±8%, means±SE, P<0.01). 5 mg kg-1 and lO mg kg-1 quinidine both decreased peak LVSP and peak dp/dt max (91±3% and 92±1%, resp., and 80±5% and 74±6% means ±SE, P<0.05). Thus, disopyramide had the most marked negative inotropic potential of the investigated class-I-antiarrhythmic drugs. The negative inotropic effects of flecainide were less pronounced, but high dosages of flecainide also caused a depression of myocardial performance. When i.v. administration of class-I antiarrhythmic drugs is necessary, the different extent of the negative inotropic side-effect should be taken into consideration, especially in patients with reduced left ventricular function.