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Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation.
- Source :
-
Pharmacological research [Pharmacol Res] 2006 Aug; Vol. 54 (2), pp. 136-41. Date of Electronic Publication: 2006 Apr 01. - Publication Year :
- 2006
-
Abstract
- It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IKACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IKACh to AF remains unknown. We investigated the role of the IKACh channel in canine AF models using tertiapin, a selective IKACh blocker. Tertiapin (4-41 nmol kg(-1), i.v.) terminated AF in the canine VNS-induced and aconitine-induced AF models. The muscarinic M-receptor antagonist AF-DX-116 terminated AF in these models, but the adenosine receptor antagonist DPCPX had no effect. Thus it is likely that IKACh activation via the M-receptor has a crucial role in both models. Tertiapin (12 nmol kg(-1), i.v.) preferentially prolonged the atrial effective refractory period (ERP) but not the ventricular ERP under the VNS condition. This peptide (4-41 nmol kg(-1), i.v.) did not affect PQ, QRS and corrected QT intervals in isoflurane-anaesthetised dogs. These results suggest that a selective IKACh blocker is effective in canine AF models without affecting ventricular repolarisation, and might be useful for the treatment of patients with AF.
- Subjects :
- Animals
Anti-Arrhythmia Agents therapeutic use
Atrial Fibrillation metabolism
Atrial Fibrillation physiopathology
Bee Venoms therapeutic use
Dogs
Dose-Response Relationship, Drug
Electrocardiography
Female
Heart Atria drug effects
Male
Anti-Arrhythmia Agents pharmacology
Atrial Fibrillation drug therapy
Bee Venoms pharmacology
Heart Atria physiopathology
Potassium Channels physiology
Refractory Period, Electrophysiological drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1043-6618
- Volume :
- 54
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 16725344
- Full Text :
- https://doi.org/10.1016/j.phrs.2006.03.021