How do different class 1 antiarrhythmic drugs affect force of contraction and maximal upstroke velocity in guinea-pig myocardium?
Class 1 antiarrhythmic drugs exhibit distinct mechanisms of negative inotropic effects, suggesting that their clinical selection should consider the patient's cardiac function.
The relationship between the negative inotropic effect and the effect on maximal upstroke velocity of action potentials (Vmax) induced by class 1 antiarrhythmic drugs aprindine (A); cibenzoline (C); disopyramide (D); lidocaine (L); pirmenol (P); quinidine (Q) was evaluated in the guinea-pig myocardium using electrophysiological techniques. Each drug reduced the force of contraction (Fc) and Vmax of fast action potentials dose-dependently. Tetrodotoxin and verapamil also decreased Fc in a dose-dependent manner. Class 1 an-tiarrhythmic drugs also reduced Vmax of the Ca-dependent slow response together with Fc. These drugs might be divided into three types according to the regression patterns of Fc. Type 1: The reduction of Fc was mainly due to Na channel blockade, resembling the pattern of tetrodotoxin (A). Drugs of this type show weaker negative inotropic than antiarrhythmic properties compared with drugs of types 2 and 3. Type 2: The reduction of Fc was predominantly due to Ca channel blockade, resembling the pattern of verapamil (Q). Type 3: Other type (C, D, L, P). This classification of class 1 antiarrhythmic drugs seems to be clinically useful in choice of drugs considering the patient's condition, such as cardiac function, and possible mechanism of arrhythmia.
Takahiro Nawada (1990) studied this question.