Comparison of the effects of IK,ACh, IKr, and INa block in conscious dogs with atrial fibrillation and on action potentials in remodeled atrial trabeculae

Viktor Juhász, Tibor Hornyik, Attila Benák, Norbert Nagy, Zoltán Husti, Róbert Pap, László Sághy, László Virág, András Varró, István Baczkó

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Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of morbidity and mortality. Traditional antiarrhythmic agents used for restoration of sinus rhythm have limited efficacy in long-term AF and they may possess ventricular proarrhythmic adverse effects, especially in patients with structural heart disease. The acetylcholine receptor-activated potassium channel (IK,ACh) represents an atrial selective target for future AF management. We investigated the effects of the IK,ACh blocker tertiapin-Q (TQ), a derivative of the honeybee toxin tertiapin, on chronic atrial tachypacing-induced AF in conscious dogs, without the influence of anesthetics that modulate a number of cardiac ion channels. Action potentials (APs) were recorded from right atrial trabeculae isolated from dogs with AF. TQ significantly and dose-dependently reduced AF incidence and AF episode duration, prolonged atrial effective refractory period, and prolonged AP duration. The reference drugs propafenone and dofetilide, both used in the clinical management of AF, exerted similar effects against AF in vivo. Dofetilide prolonged atrial AP duration, whereas propafenone increased atrial conduction time. TQ and propafenone did not affect the QT interval, whereas dofetilide prolonged the QT interval. Our results show that inhibition of IK ,ACh may represent a novel, atrial-specific target for the management of AF in chronic AF.

Original languageEnglish
Pages (from-to)18-25
Number of pages8
JournalCanadian journal of physiology and pharmacology
Volume96
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Atrial fibrillation
  • Conscious dog
  • I
  • Propafenone
  • Tertiapin-Q

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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