Electrophysiological effects of tocainide on canine subendocardial Purkinje fibers surviving infarction

Abstract

The effects of 10 and 20 mg/l of tocainide on transmembrane action potential characteristics were examined in Purkinje fibers surviving infarction. Infarcted tissue was obtained from canine hearts 24 h after coronary artery ligation. The preparation was stimulated at basic cycle lengths (BCL) of 1000-300 ms. Tocainide reduced the overshoot and amplitude of Purkinje fibers surviving infarction. The maximum upstroke velocity (V̇(max)) was decreased by tocainide in a dose dependent manner. This effect was more prominent at the shorter BCL. Statistical analysis revealed a significant interaction of the BCL with the drug effect on overshoot, amplitude, V̇(max) and action potential durations (APD50(%) and APD90(%)). Tocainide reduced the effective refractory period (ERP) at the BCL of 1000 ms, but had no significant effect at the BCL of 300 ms. Membrane responsiveness and steady state characteristics of V̇(max) were shifted significantly to more negative membrane potentials by tocainide. Investigation of the recovery kinetics of V̇(max) in the presence of tocainide showed an exponential recovery of V̇(max) with a time constant of 514 ms. These results support the finding that the effect of tocainide on V̇(max) and conduction is enhanced at faster rates of stimulation. Thus tocainide may be able to depress conduction to produce bidirectional block in the termination of ventricular tachycardia caused by reentry, while having minimal effect on conduction at normal heart rates.