Effects of flecainide on the rate dependence of atrial refractoriness, atrial repolarization and atrioventricular node conduction in anesthetized dogs

O’Hara, Gilles; Villemaire, Christine; Talajic, Mario; Nattel, Stanley

doi:10.1016/0735-1097(92)90342-k

Cited by 25 publications

(6 citation statements)

References 40 publications

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“…20,34 A flecainide-induced reduction in aERP accommodation to atrial activation rates, which may be important in suppressing AF, has been demonstrated by others. 18,[34][35][36] However, this mechanism of rate-dependency and increased drug action at rapid atrial activation rates could not be proven by the present study. Still, despite the lack of aERP prolongation at the atrial rates measured in the present study, we cannot rule out possible increases in 136.…”

Section: Discussioncontrasting

confidence: 69%

“…In humans, some reported a slight but not significant flecainide‐induced increase in aERP, whereas others reported significant and use‐dependent increases 20, 34. A flecainide‐induced reduction in aERP accommodation to atrial activation rates, which may be important in suppressing AF, has been demonstrated by others 18, 34, 35, 36. However, this mechanism of rate‐dependency and increased drug action at rapid atrial activation rates could not be proven by the present study.…”

Section: Discussionmentioning

confidence: 90%

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Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

Haugaard

Pehrson

Carstensen

et al. 2014

Veterinary Internal Medicne

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BackgroundOnly few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood.ObjectivesTo study the potential of flecainide to terminate acutely induced AF of short duration (≥15 minutes), to examine flecainide‐induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization.AnimalsNine Standardbred horses. Eight received flecainide, 3 were used as time‐matched controls, 2 of which also received flecainide.MethodsProspective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing‐induced AF (≥15 minutes), and drug‐induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods.ResultsFlecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected.Conclusions and Clinical ImportanceFlecainide had clear antiarrhythmic properties in terminating acute pacing‐induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 90%

Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

Haugaard

Pehrson

Carstensen

et al. 2014

Veterinary Internal Medicne

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“…11 Katritsis et al also reported that flecainide prolonged atrial ERP during sinus rhythm, but not during atrial pacing at any heart rate. 12 O'Hara et al 13 and Hodess et al 14 reported that atrial ERP prolongation was more pronounced when flecainide was administered in dogs with pharmacological autonomic nerve block. Although we did not compare the effects in the presence or absence of autonomic nerve block, the sympathetic nerve activity in the present study was expected to be low because of the deep sedation induced by administration of midazolam and fentanyl.…”

Section: Discussionmentioning

confidence: 99%

Frequency-Dependent Electrophysiological Effects of Flecainide, Nifekalant and <i>d,l</i>-Sotalol on the Human Atrium

Watanabe

Nakai

et al. 2001

Jpn Circ J

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To compare the effects of class Ic and III antiarrhythmic agents on the termination and prevention of atrial fibrillation, the present study investigated the use-dependent electrophysiological effects of flecainide, nifekalant and d,l-sotalol on the human atrium. Flecainide significantly prolonged effective refractory period (ERP), intra-atrial conduction time (IACT) and monophasic action potential duration (MAPD), and its effects on ERP and IACT were use-dependent. Nifekalalant significantly prolonged ERP and MAPD, and these effects were reverse usedependent; however, there was no significant change in IACT. d,l-Sotalol significantly prolonged MAPD and the effect was reverse use-dependent. It significantly prolonged ERP, but the effect was not reverse use-dependent. d,l-Sotalol increased IACT in a use-dependent manner. Thus, for atrial fibrillation, class Ic antiarrhythmic agents might be more effective in termination and class III antiarrhythmic agents might be more effective in prevention. (Jpn Circ J 2001; 65: 1 -6)

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“…41 Flecainide also suppresses atrial APD accommodation to heart rate changes in anaesthetized dogs, leading to rate-dependent prolongation of atrial refractoriness, which may be important in suppressing AF. 42 In an experimental canine models of AF, flecainide terminates AF by causing a tachycardia-dependent increase in atrial effective refractory period and wavelength, reducing the number of re-entrant circuits, so that the arrhythmia can no longer sustain itself. 43,44 However, in goats instrumented with multiple atrial electrodes, cardioversion of sustained AF induced by flecainide could not be attributed to a prolongation of atrial wavelength but to a progressive widening in the temporal excitable gap during AF.…”

Section: Focus On Flecainidementioning

confidence: 99%

Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation

et al. 2010

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Atrial fibrillation (AF) is the most common arrhythmia in clinical practise and its prevalence is increasing. Over the last 25 years, flecainide has been used extensively worldwide, and its capacity to reduce AF symptoms and provide long-term restoration of sinus rhythm (SR) has been well documented. The increased mortality seen in patients treated with flecainide in the Cardiac Arrhythmia Suppression Trial (CAST) study, published in 1991, still deters many clinicians from using flecainide, denying many new AF patients a valuable treatment option. There is now a body of evidence that clearly demonstrates that flecainide has a favourable safety profile in AF patients without significant left ventricular disease or coronary heart disease. As a result of this evidence, flecainide is now recommended as one of the first-line treatment options for restoring and maintaining SR in patients with AF under current treatment guidelines. The objective of this article is to review the literature pertaining to the pharmacological characteristics, safety and efficacy of flecainide, and to place this drug in the context of current therapeutic management strategies for AF.

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Effects of flecainide on the rate dependence of atrial refractoriness, atrial repolarization and atrioventricular node conduction in anesthetized dogs

Cited by 25 publications

References 40 publications

Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

Frequency-Dependent Electrophysiological Effects of Flecainide, Nifekalant and <i>d,l</i>-Sotalol on the Human Atrium

Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation

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