Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs
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- Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs
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Jonas Goldin Diness, Lasse Skibsbye, Rafel Simó-Vicens, Joana Louro Larupa dos Santos, Pia Rengtved Lundegaard, Carlotta Citerni, Daniel Rafael Peter Sauter, Sofia Hammami Bomholtz, Jesper Hastrup Svendsen, Søren-Peter Olesen, Ulrik S Sørensen, Thomas Jespersen, Morten Grunnet, Bo Hjorth Bentzen
Methods and Results A total of 43 pigs were used for the studies. AF reversion in conscious long-term tachypaced pigs: Pigs were subjected to atrial tachypacing (7 Hz) until they developed sustained AF that could not be reverted by vernakalant 4 mg/kg (18.8±3.3 days of atrial tachypacing). When the SK channel inhibitor AP14145 was tested in these animals, vernakalant-resistant AF was reverted to sinus rhythm, and reinduction of AF by burst pacing (50 Hz) was prevented in 8 of 8 pigs. Effects on refractory period and AF duration in open chest pigs: The effects of AP14145 and vernakalant on the effective refractory periods and acute burst pacing-induced AF were examined in anaesthetized open chest pigs. Both vernakalant and AP14145 significantly prolonged atrial refractoriness and reduced AF duration without affecting the ventricular refractoriness or blood pressure in pigs subjected to 7 days atrial tachypacing, as well as in sham-operated control pigs.
Conclusions SK currents play a role in porcine atrial repolarization, and pharmacological inhibition of these with AP14145 demonstrates antiarrhythmic effects in a vernakalant-resistant porcine model of AF. These results suggest SK channel blockers as potentially interesting anti-AF drugs.
|Journal||Circulation: Arrhythmia and Electrophysiology|
|Number of pages||19|
|Publication status||Published - 10 Oct 2017|
- The Faculty of Health and Medical Sciences - Atrial Fibrillation, Blood Pressure, Heart Atria, Swine, vernakalant, small conductance calcium-activated potassium channels, AP14145
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