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Comparison of the effects of I K,ACh , I Kr , and I Na block in conscious dogs with atrial fibrillation and on action potentials in remodeled atrial trabeculae.
- Source :
-
Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2018 Jan; Vol. 96 (1), pp. 18-25. Date of Electronic Publication: 2017 Sep 11. - Publication Year :
- 2018
-
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 (I <subscript>K,ACh</subscript> ) represents an atrial selective target for future AF management. We investigated the effects of the I <subscript>K,ACh</subscript> 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 I <subscript>K</subscript> <subscript>,ACh</subscript> may represent a novel, atrial-specific target for the management of AF in chronic AF.
- Subjects :
- Animals
Atrial Fibrillation physiopathology
Bee Venoms administration & dosage
Bee Venoms pharmacology
Bee Venoms therapeutic use
Dogs
Electrocardiography
Heart Atria drug effects
Male
Phenethylamines administration & dosage
Phenethylamines pharmacology
Phenethylamines therapeutic use
Potassium Channel Blockers administration & dosage
Potassium Channel Blockers pharmacology
Propafenone administration & dosage
Propafenone pharmacology
Propafenone therapeutic use
Refractory Period, Electrophysiological drug effects
Sulfonamides administration & dosage
Sulfonamides pharmacology
Sulfonamides therapeutic use
Action Potentials drug effects
Atrial Fibrillation drug therapy
Atrial Remodeling drug effects
Consciousness drug effects
Heart Atria physiopathology
Potassium Channel Blockers therapeutic use
Potassium Channels metabolism
Receptors, Cholinergic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1205-7541
- Volume :
- 96
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Canadian journal of physiology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28892643
- Full Text :
- https://doi.org/10.1139/cjpp-2017-0342