Negative Inotropic Effects of Class I Antiarrhythmics on Guinea Pig Ventricular Myocardium: Correlation with L-Type Ca²⁺ Channel Blockade

Abstract

The negative inotropic effects of nine Vaughan Williams class I antiarrhythmic drugs were examined in guinea pig ventricular tissue preparations. The drugs decreased the contractile force of papillary muscles with different potencies: the potency order was propafenone > aprindine > cibenzoline > flecainide > ranolazine > disopyramide > pilsicainide > mexiletine > GS-458967. The potency of drugs correlated with the reported IC₅₀ values to block the L-type Ca²⁺ channel rather than the Na⁺ channel. The effects of drugs were roughly the same when examined under a high extracellular K⁺ solution, which inactivates the Na⁺ channel. Furthermore, the attenuation of the extracellular Ca²⁺-induced positive inotropy was strong with propafenone, moderate with cibenzoline, and weak with pilsicainide. These results indicate that the negative inotropic effects of class I antiarrhythmic drugs can be largely explained by their blockade of the L-type Ca²⁺ channel.