Electrophysiologic effects of the new Class III antiarrhythmic drug dofetilide compared to the class IA antiarrhythmic drug quinidine in experimental canine atrial flutter: Role of dispersion of refractoriness in antiarrhythmic efficacy

Yong-Mei Cha, Alan Wales, Paul Wolf, Shahin Shahrokni, Neil Sawhney, Gregory K. Feld

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32 Citations (Scopus)

Abstract

Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studies suggest that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference ≤ 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200- msec cycle length (P < 0.001) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≤ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

Original languageEnglish (US)
Pages (from-to)809-827
Number of pages19
JournalJournal of Cardiovascular Electrophysiology
Volume7
Issue number9
StatePublished - 1996
Externally publishedYes

Fingerprint

Atrial Flutter
Quinidine
Anti-Arrhythmia Agents
Canidae
Dogs
Electrodes
Pharmaceutical Preparations
dofetilide
Cardiac Arrhythmias

Keywords

  • atrial flutter
  • dispersion of refractory period
  • dofetilide
  • quinidine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

@article{82c1810ed02042e4a6c8e6abfd7eea76,
title = "Electrophysiologic effects of the new Class III antiarrhythmic drug dofetilide compared to the class IA antiarrhythmic drug quinidine in experimental canine atrial flutter: Role of dispersion of refractoriness in antiarrhythmic efficacy",
abstract = "Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studies suggest that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23{\%}, slowed CV by 9{\%} at 200-msec cycle length (P < 0.001) and by 39{\%} at 150-msec cycle length (P < 0.001), and increased wavelength by 11{\%} (P < 0.02). Dofetilide reduced dispersion of ERP by 20{\%} (P = 0.003) and adjacent electrodes with ERP difference ≤ 20 msec by 76{\%} (P < 0.001). Dofetilide slowed atrial flutter by 37{\%} (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14{\%} (P < 0.001), slowed CV by 14{\%} at 200- msec cycle length (P < 0.001) and by 19{\%} at 150-msec cycle length (P < 0.001), and reduced wavelength by 2{\%} (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57{\%} (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≤ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.",
keywords = "atrial flutter, dispersion of refractory period, dofetilide, quinidine",
author = "Yong-Mei Cha and Alan Wales and Paul Wolf and Shahin Shahrokni and Neil Sawhney and Feld, {Gregory K.}",
year = "1996",
language = "English (US)",
volume = "7",
pages = "809--827",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
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number = "9",

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TY - JOUR

T1 - Electrophysiologic effects of the new Class III antiarrhythmic drug dofetilide compared to the class IA antiarrhythmic drug quinidine in experimental canine atrial flutter

T2 - Role of dispersion of refractoriness in antiarrhythmic efficacy

AU - Cha, Yong-Mei

AU - Wales, Alan

AU - Wolf, Paul

AU - Shahrokni, Shahin

AU - Sawhney, Neil

AU - Feld, Gregory K.

PY - 1996

Y1 - 1996

N2 - Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studies suggest that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference ≤ 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200- msec cycle length (P < 0.001) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≤ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

AB - Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studies suggest that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference ≤ 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200- msec cycle length (P < 0.001) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≤ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

KW - atrial flutter

KW - dispersion of refractory period

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KW - quinidine

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