title: Diverse electrophysiologic effects of propafenone and flecainide in canine Purkinje fibers: implications for antiarrhythmic drug classification.
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 microM) 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 microM; 59 +/- 10% vs. 24 +/- 4% at 5 microM). Use-dependent block onset and dissipation were significantly slower for flecainide than for propafenone (e.g., at 1 microM 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 model of use dependency. Predictions approximated the experimentally results only for flecainide. At 1 microM, propafenone shortened action potential duration at all rates; flecainide had biphasic effects. At 5 microM, the effect of flecainide was similar to that of 1 microM propafenone. Thus, in Purkinje fibers, the kinetics of use-dependent local anesthetic effects and the effects on repolarization discriminate flecainide from propafenone.
authors.affiliation: Dipartimento di Fisiologia e Biochimica Generali, Universitá degli Studi di Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zaza
authors.forename: G
authors.initials: G
authors.lastname: Malfatto
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification*; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D011405:Propafenone / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D011405:Propafenone; D005424:Flecainide