title: Influence of duration of rapid ventricular pacing on ventricular refractoriness in the presence of propafenone and lidocaine.
abstract: Propafenone and lidocaine have a rate dependent negative dromotropic effect on intraventricular conduction. We investigated the use dependent actions of propafenone and lidocaine on intraventricular conduction in isolated guinea pig hearts perfused by the method of Langendorff. Of primary interest was how the number of stimuli of the conditioning train (S1) might influence the ventricular effective refractory period (VERP) when refractoriness is assessed at a high pacing rate. Propafenone (0.3 microM) and lidocaine (50 microM) caused a comparable prolongation of the intraventricular conduction time during sinus rhythm. During ventricular pacing in the presence of propafenone an abrupt decrease of the pacing cycle length (220 to 120 ms) resulted in an initial peak of rate dependent prolongation of the QRS interval that subsequently decreased to a stable steady-state level. Lidocaine also induced a rate dependent increase of the intraventricular conduction time up to a steady-state level. The time constant, characterizing the changes of the intraventricular conduction time after shortening the ventricular pacing cycle length from 220 to 120 ms was significantly (P < 0.01) longer in the presence of propafenone (tau = 31 +/- 4 beats; mean +/- SEM; n = 11) than for lidocaine (tau = 3 +/- 1; n = 10). Both drugs caused the greatest increase of the VERP when the number of conditioning stimuli (S1, interstimulus interval = 120 ms) was in the range of their respective time constant. However, when the number of conditioning stimuli was further increased, VERP progressively diminished. These effects may be explained by a shortening of the action potential during high rates that results in a decreased binding of propafenone to Na+ channels and by the direct shortening of repolarization period by lidocaine (Class IB drug).
authors.affiliation: Department of Internal Medicine, Karl Franzens-University, Graz, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Stark
authors.forename: G
authors.initials: G
authors.lastname: Stark
authors.forename: K
authors.initials: K
authors.lastname: Kasper
authors.forename: I
authors.initials: I
authors.lastname: Schwarzl
authors.forename: M
authors.initials: M
authors.lastname: Decrinis
authors.forename: E
authors.initials: E
authors.lastname: Pilger
authors.forename: H A
authors.initials: HA
authors.lastname: Tritthart
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate; D006352:Heart Ventricles / Q000294:innervation; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D011405:Propafenone / Q000008:administration & dosage / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D012044:Regression Analysis; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D011405:Propafenone; D008012:Lidocaine