Diverse electrophysiologic effects of propafenone and flecainide in canine Purkinje fibers: Implications for antiarrhythmic drug classification

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Abstract

Propafenone and flecainide are assigned to class Ic of the Campbell- Vaughan Williams classification because of their effects on ventricular muscle. The authors compared the use-dependent local anesthetic properties and the effects on repolarization of these drugs (1 and 5 μM) in Purkinje fibers. A reduction in maximum upstroke velocity was used as an index of the local anesthetic action. The rate dependency of the drug's effects on repolarization was evaluated by analyzing the relationship between action potential duration during steady-state stimulation and cycle length (CL). Tonic block was higher for propafenone (n = 10) than for flecainide (n = 7) at both concentrations tested (19 ± 3% vs. 4 ± 1% at 1 μM; 59 ± 10% vs. 24 ± 4% at 5 μM). Use-dependent block onset and dissipation were significantly slower for flecainide than for propafenone (e.g., at 1 μM and CL = 500 ms, time constant of block onset = 31 ± 6 vs. 9 ± 1 beats; time constant of recovery from block = 7.7 ± 0.2 vs. 2.8 ± 0.2 sec; P <.05). Steady-state block measured at each CL was compared with that predicted by a theoretical mode use dependency. Predictions approximated the experimentally results only for flecainide. At 1 μM, propafenone shortened action potential duration at all rates; flecainide had biphasic effects. At 5 μM, the effect of flecainide was similar to that of 1 μM propafenone. Thus, in Purkinje fibers, the kinetics of use-dependent local anesthetic effects and the effects on repolarization discriminate flecainide from propafenone.

Original languageEnglish
Pages (from-to)336-343
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number1
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Pharmacology

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