The interaction of cycle length with the electrophysiological effect of lidocaine, tocainide and verapamil on canine purkinje fibers

Intracellular action potentials were recorded from normal canine Purkinje fibers using the standard microelectrode technique. The effects of lidocaine (2 and 5 mg/1), tocainide (10 and 20 mg/1) and verapamil (0.5 and 1.0 mg/1) on action potential characteristics as well as conduction times were measured at cycle lengths of 1000, 800, 600, 500, 400 and 300 ms. Lidocaine and tocainide shortened APD50 % and APD90 %, and verapamil shortened APD50 % and lengthened APD90 %. All of these effects were greatest at the longest cycle lengths. A similar interaction of changes in ERP with cycle length was observed for lidocaine and tocainide. Verapamil increased ERP but this effect was not significant. Tocainide and verapamil reduced dV/dtmax while lidocaine had no significant effect. All three drugs increased conduction time. This effect was accentuated at shorter cycle lengths. No direct relationship between dV/dtmax and conduction times were observed. These results indicate that many of the electrophysiological effects of lidocaine, tocainide and verapamil are modified by cycle length. We propose that future studies on the electrophysiology of antiarrhythmic drugs should include stimulation both at long and short cycle lengths.