Effects of Antiarrhythmic Drugs on Premature Action Potential Duration in Canine Ventricular Muscle Fibers

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Abstract
The range of premature action potential durations (APDs) during the first 100 ms of electrical restitution was determined in canine ventricular muscle fibers (VM) in the presence of lidocaine (4 and 8 .mu.g/ml), mexiletine (8 .mu.g/ml), flecainide (2 and 4 .mu.g/ml), procainamide (50 .mu.g/ml), quinidine (10 .mu.g/ml), and disopyramide (10 .mu.g/ml). The drug effects on the characteristics of action potential at the basic cycle lengths (BCLs) of 500 and 1,000 ms were similar to those reported previously. At control, the range of premature APDs was .apprx. 40 ms at BCL of 1,000 ms and .apprx. 30 ms at BCL of 500 ms. It was decreased 26-52% by lidocaine, mexiletine, and flecainide, not changed significantly by procainamide, and increased 17-53% by quinidine and disopyramide. The range of premature APDs at control and in the presence of drugs in ventricular muscle was smaller than in Purkinje fibers at the same or lower drug concentrations (Varro et al., J Pharmacol Exp Ther 1985;233:304). The four factors influencing the premature APD range in the Purkinje fibers operated in the VM as follows: The difference between the duration of effective refractory period (ERP) and the APD at BCL (APDb) (i.e., the ERP-APDb interval) was increased by lidocaine, mexiletine, and flecainide; normalized restitution curve was shifted toward longer premature APD values only by flecainide; the kinetics of restitution were slowed only by procainamide; and APD at BCL of 1,000 ms was shortened by lidocaine and mexiletine, and prolonged at BCLs of 1,000 and 500 ms by the other four drugs. Unlike the Purkinje fibers, the range of premature APDs in VM was influenced chiefly by APD at BCL. The lengthening of the premature APD range by quinidine and disopyramide suggests that these drugs may be expected to increase dispersion of repolarization during the propagation of an early premature impulse, and that this increase may be greater at long than at short BCL.