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 (2 mg, 4 mg and 8 mg kg-1) with disopyramide (1 mg, 4 mg and 8 mg kg-1), quinidine (5 mg and 10 mg kg-1) and saline (controls). Isovolumic measurements of ventricular function by short aortic crossclamping were performed in 82 open-chest 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 less than 0.01), 2 mg 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 less than 0.05, peak dp/dt max 64 +/- 7%, P less than 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 less than 0.01). 5 mg kg-1 and 10 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 less than 0.05). Thus, disopyramide had the most marked negative inotropic potential of the investigated class-I-antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)