1. Negative Inotropic Effects of Class I Antiarrhythmics on Guinea Pig Ventricular Myocardium: Correlation with L-Type Ca 2+ Channel Blockade.
- Author
-
Hiiro H, Hashimoto T, Mizoguchi M, Kaneko M, Deguchi N, Takahashi Y, Hamaguchi S, Namekata I, and Tanaka H
- Subjects
- Guinea Pigs, Animals, Myocardium, Lidocaine pharmacology, Papillary Muscles, Anti-Arrhythmia Agents pharmacology, Propafenone pharmacology
- 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 IC
50 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.- Published
- 2023
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