Relationship between negative inotropic and chronotropic effects of tocainide and five class I antiarrhythmic drugs in the coronary perfused guinea-pig heart.
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. 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) = aprinidine (Apr) > mexiletine (Mex) > lidocaine (Lid) > disopyramide (Dis) > tocainide (Toc); and the order of negative chronotropic effect was: Apr > Qui > Mex > Dis > Lid > Toc. 3. The order of the negative inotropic potency relative to chronotropic effect (expressed as a ratio: ID50 for Fc/ID50 for HR) was Lid > Qui > Dis > Toc > Mex > Apr (n = 6). 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: ID50 for Fc in driven heart/ID50 for spontaneously beating HR) was: Mex > Apr > Toc > Dis > Qui > Lid (n = 6). 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.
Matsumoto
T
T
Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Hasegawa
J
J
Mashiba
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D016677:Tocainide / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D016677:Tocainide