Relationship between use-dependent effects of antiarrhythmic drugs on conduction and Vmax in canine cardiac Purkinje fibers

The purpose of these experiments was to evaluate the relationship between interval dependent effects of antiarrhythmic drugs on conduction time and Vmax in canine cardiac Purkinje fibers. Standard microelectrode techniques were used to monitor action potential characteristics at two sites along a canine cardiac false tendon and to measure interelectrode conduction time. The maximum rate of voltage rise during phase 0 (Vmax) and conduction time were independent of diastolic interval under control conditions. In the presence of local anesthetic drugs, recovery from drug-induced depression of Vmax and conduction were first order processes with recovery time constants (mean +/- S.D. in seconds) of 0.14 +/- 0.02 (for Vmax) and 0.15 +/- 0.04 (for conduction time) for lidocaine; 0.17 +/- 0.04 and 0.18 +/- 0.05, respectively, for mexiletine; 0.26 +/- 0.05 and 0.27 +/- 0.07 for amitriptyline; and 1.01 +/- 0.31 and 1.00 +/- 0.32 for procainamide. The kinetics of onset of block were studied using a 30-sec pause, followed by a pacing cycle length of 300 msec (for procainamide) or 1 sec (for quinidine). The onset time constants averaged 2.66 +/- 0.53 pulses (for Vmax) and 2.49 +/- 0.42 pulses (for conduction time) in the presence of procainamide; and 4.02 +/- 1.33 pulses (for Vmax) and 3.86 +/- 1.22 pulses (for conduction time) in the presence of quinidine. These experiments show that local anesthetic drugs produce use dependent changes in conduction time in vitro with time constants comparable to simultaneously measured time constants for effects on Vmax. They imply that the use dependence of drug effects on cardiac conduction can be studied quantitatively in vivo by studying the response to changes in activation frequency.