Relationship between negative inotropic and chronotropic effects of tocainide and five class I antiarrhythmic drugs in the coronary perfused guinea-pig heart

Abstract

1. 1. The relationship between the negative inotropic and chronotropic effects of tocainide and 5 other class I antiarrhythmic drugs was evaluated in Langendorff-perfused guinea-pig hearts. 2. 2. All 6 drugs reduced the contractile force (Fc) and the heart rate (HR) of spontaneously beating guinea-pig hearts in a dose-dependent manner. The order of crude negative inotropic potency was: quinidine (Qui) = aprindine (Apr) > mexiletine (Mex) > lidocaine (Lid) > disopyramide (Dis) > tocainide (Toc); and the order of negative chronotropic effect was: Apr > Qui > Mex > Dis > Lid > Toc. 3. 3. The order of the negative inotropic potency relative to chronotropic effect (expressed as a ratio: ID 50 for Fc/ID 50 for HR) was Lid > Qui > Dis > Toc > Mex > Apr ( n = 6). 4. 4. For heart electrically stimulated at a constant rate, the order of crude negative inotropic potency was: Apr > Qui > Mex > Dis > Lid > Toc, and the order of negative inotropic potency (determined by the ratio: ID 50 for Fc in driven heart/ID 50 for spontaneously beating HR) was: Mex > Apr > Toc > Dis > Qui > Lid ( n = 6). 5. 5. There was a significant influence of negative chronotropic effect on the inotropic potency and the order was: Lid > Qui > Dis > Toc > Apr > Mex. The potency of various drugs is clinically useful in the choice of drugs when considering cardiac function and heart rate.