Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration?

The prolongation of the action potential duration (APD) induced by sotalol has been shown to be diminished with increasing heart rate. This phenomenon is called "reverse use dependence." We examined the Ia, Ib, and Ic effects of different Class I drugs on the APD under normal and fast stimulation rates (1.0 and 2.5 Hz) in isolated rabbit atrial and ventricular muscles by means of intracellular microelectrodes. Results (n = 98): With 1.0 Hz lidocaine (Ib, 4.3 x 10(-5) M) shortened the APD at 90% repolarization (APD90) in the atrium by 9% and in the ventricle by 8% (NS), whereas quinidine (Ia, 2.2 x 10(-5) M) and prajmaline (Ia, 10(-6) M) prolonged the APD90 in the atrium (quinidine +45%; prajmaline +10%, P < 0.001) and in the ventricle (+42%, P < 0.001; +17%, P < 0.05). Propafenone (Ic, 2.6 x 10(-6) M) showed this effect only in the atrium (APD90 +33%; P < 0.01). With the faster stimulation rate of 2.5 Hz we could not find a significant influence of any drug on the APD90 in the ventricle and only quinidine prolonged the APD90 in the atrium by 16% (P < 0.05).

The subclassification of Class I antiarrhythmic drugs that is based on APD modifying influences is only valid under normal heart rates (1.0 Hz). During tachycardia these actions are absent and the phenomenon of "reverse use dependence" is found in Class I drugs. Therefore, an additional antiarrhythmic effect due to APD modification by the examined drugs should not be expected at rapid heart rates.