Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs. / Diness, Jonas Goldin; Skibsbye, Lasse; Simó-Vicens, Rafel; Louro Larupa dos Santos, Joana; Lundegaard, Pia Rengtved; Citerni, Carlotta; Sauter, Daniel Rafael Peter; Bomholtz, Sofia Hammami; Svendsen, Jesper Hastrup; Olesen, Søren-Peter; Sørensen, Ulrik S; Jespersen, Thomas; Grunnet, Morten; Bentzen, Bo Hjorth.

I: Circulation: Arrhythmia and Electrophysiology, Bind 10, e005125, 10.10.2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Diness, JG, Skibsbye, L, Simó-Vicens, R, Louro Larupa dos Santos, J, Lundegaard, PR, Citerni, C, Sauter, DRP, Bomholtz, SH, Svendsen, JH, Olesen, S-P, Sørensen, US, Jespersen, T, Grunnet, M & Bentzen, BH 2017, 'Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs', Circulation: Arrhythmia and Electrophysiology, bind 10, e005125. https://doi.org/10.1161/CIRCEP.117.005125

APA

Diness, J. G., Skibsbye, L., Simó-Vicens, R., Louro Larupa dos Santos, J., Lundegaard, P. R., Citerni, C., ... Bentzen, B. H. (2017). Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs. Circulation: Arrhythmia and Electrophysiology, 10, [e005125]. https://doi.org/10.1161/CIRCEP.117.005125

Vancouver

Diness JG, Skibsbye L, Simó-Vicens R, Louro Larupa dos Santos J, Lundegaard PR, Citerni C o.a. Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs. Circulation: Arrhythmia and Electrophysiology. 2017 okt 10;10. e005125. https://doi.org/10.1161/CIRCEP.117.005125

Author

Diness, Jonas Goldin ; Skibsbye, Lasse ; Simó-Vicens, Rafel ; Louro Larupa dos Santos, Joana ; Lundegaard, Pia Rengtved ; Citerni, Carlotta ; Sauter, Daniel Rafael Peter ; Bomholtz, Sofia Hammami ; Svendsen, Jesper Hastrup ; Olesen, Søren-Peter ; Sørensen, Ulrik S ; Jespersen, Thomas ; Grunnet, Morten ; Bentzen, Bo Hjorth. / Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs. I: Circulation: Arrhythmia and Electrophysiology. 2017 ; Bind 10.

Bibtex

@article{c365007a95cd4ec784645af50bd3edae,
title = "Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs",
abstract = "Background Evidence has emerged that small-conductance Ca2+-activated K+ (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited by ventricular adverse effects and efficacy loss as AF progresses.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.",
keywords = "The Faculty of Health and Medical Sciences, Atrial Fibrillation, Blood Pressure, Heart Atria, Swine, vernakalant, small conductance calcium-activated potassium channels, AP14145",
author = "Diness, {Jonas Goldin} and Lasse Skibsbye and Rafel Sim{\'o}-Vicens and {Louro Larupa dos Santos}, Joana and Lundegaard, {Pia Rengtved} and Carlotta Citerni and Sauter, {Daniel Rafael Peter} and Bomholtz, {Sofia Hammami} and Svendsen, {Jesper Hastrup} and S{\o}ren-Peter Olesen and S{\o}rensen, {Ulrik S} and Thomas Jespersen and Morten Grunnet and Bentzen, {Bo Hjorth}",
year = "2017",
month = "10",
day = "10",
doi = "10.1161/CIRCEP.117.005125",
language = "English",
volume = "10",
journal = "Circulation: Arrhythmia and Electrophysiology",
issn = "1941-3149",
publisher = "Lippincott Williams & Wilkins",

}

RIS

TY - JOUR

T1 - Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca2+-Activated K+ Channels in Pigs

AU - Diness, Jonas Goldin

AU - Skibsbye, Lasse

AU - Simó-Vicens, Rafel

AU - Louro Larupa dos Santos, Joana

AU - Lundegaard, Pia Rengtved

AU - Citerni, Carlotta

AU - Sauter, Daniel Rafael Peter

AU - Bomholtz, Sofia Hammami

AU - Svendsen, Jesper Hastrup

AU - Olesen, Søren-Peter

AU - Sørensen, Ulrik S

AU - Jespersen, Thomas

AU - Grunnet, Morten

AU - Bentzen, Bo Hjorth

PY - 2017/10/10

Y1 - 2017/10/10

N2 - Background Evidence has emerged that small-conductance Ca2+-activated K+ (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited by ventricular adverse effects and efficacy loss as AF progresses.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.

AB - Background Evidence has emerged that small-conductance Ca2+-activated K+ (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited by ventricular adverse effects and efficacy loss as AF progresses.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.

KW - The Faculty of Health and Medical Sciences

KW - Atrial Fibrillation

KW - Blood Pressure

KW - Heart Atria

KW - Swine

KW - vernakalant

KW - small conductance calcium-activated potassium channels

KW - AP14145

U2 - 10.1161/CIRCEP.117.005125

DO - 10.1161/CIRCEP.117.005125

M3 - Journal article

VL - 10

JO - Circulation: Arrhythmia and Electrophysiology

JF - Circulation: Arrhythmia and Electrophysiology

SN - 1941-3149

M1 - e005125

ER -

ID: 184612833