Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation. / Kirchhoff, Jeppe Egedal; Diness, Jonas Goldin; Abildgaard, Lea; Sheykhzade, Majid; Grunnet, Morten; Jespersen, Thomas.

In: Pfluegers Archiv, Vol. 468, No. 11, 08.10.2016, p. 1853–1863.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Kirchhoff, JE, Diness, JG, Abildgaard, L, Sheykhzade, M, Grunnet, M & Jespersen, T 2016, 'Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation', Pfluegers Archiv, vol. 468, no. 11, pp. 1853–1863. https://doi.org/10.1007/s00424-016-1883-9

APA

Kirchhoff, J. E., Diness, J. G., Abildgaard, L., Sheykhzade, M., Grunnet, M., & Jespersen, T. (2016). Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation. Pfluegers Archiv, 468(11), 1853–1863. https://doi.org/10.1007/s00424-016-1883-9

Vancouver

Kirchhoff JE, Diness JG, Abildgaard L, Sheykhzade M, Grunnet M, Jespersen T. Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation. Pfluegers Archiv. 2016 Oct 8;468(11):1853–1863. https://doi.org/10.1007/s00424-016-1883-9

Author

Kirchhoff, Jeppe Egedal ; Diness, Jonas Goldin ; Abildgaard, Lea ; Sheykhzade, Majid ; Grunnet, Morten ; Jespersen, Thomas. / Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation. In: Pfluegers Archiv. 2016 ; Vol. 468, No. 11. pp. 1853–1863.

Bibtex

@article{1279209d96d246628e824ea58e3ccb99,
title = "Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation",
abstract = "Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca(2+)-activated K(+) (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect. The duration of AF was reduced with otherwise subefficacious concentrations of either dofetilide or amiodarone when combined with ICA, also at a subefficacious concentration. At a concentration level effective as monotherapy, dofetilide produced a marked increase in the QT interval. This QT prolonging effect was absent when combined with ICA at non-efficacious monotherapy concentrations. The results thereby reveal that combination of subefficacious concentrations of an SK channel blocker and either dofetilide or amiodarone can maintain anti-AF properties, while the risk of ventricular arrhythmias is reduced.",
author = "Kirchhoff, {Jeppe Egedal} and Diness, {Jonas Goldin} and Lea Abildgaard and Majid Sheykhzade and Morten Grunnet and Thomas Jespersen",
year = "2016",
month = "10",
day = "8",
doi = "10.1007/s00424-016-1883-9",
language = "English",
volume = "468",
pages = "1853–1863",
journal = "Pfl{\"u}gers Archiv - European Journal of Physiology",
issn = "0031-6768",
publisher = "Springer",
number = "11",

}

RIS

TY - JOUR

T1 - Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation

AU - Kirchhoff, Jeppe Egedal

AU - Diness, Jonas Goldin

AU - Abildgaard, Lea

AU - Sheykhzade, Majid

AU - Grunnet, Morten

AU - Jespersen, Thomas

PY - 2016/10/8

Y1 - 2016/10/8

N2 - Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca(2+)-activated K(+) (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect. The duration of AF was reduced with otherwise subefficacious concentrations of either dofetilide or amiodarone when combined with ICA, also at a subefficacious concentration. At a concentration level effective as monotherapy, dofetilide produced a marked increase in the QT interval. This QT prolonging effect was absent when combined with ICA at non-efficacious monotherapy concentrations. The results thereby reveal that combination of subefficacious concentrations of an SK channel blocker and either dofetilide or amiodarone can maintain anti-AF properties, while the risk of ventricular arrhythmias is reduced.

AB - Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca(2+)-activated K(+) (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect. The duration of AF was reduced with otherwise subefficacious concentrations of either dofetilide or amiodarone when combined with ICA, also at a subefficacious concentration. At a concentration level effective as monotherapy, dofetilide produced a marked increase in the QT interval. This QT prolonging effect was absent when combined with ICA at non-efficacious monotherapy concentrations. The results thereby reveal that combination of subefficacious concentrations of an SK channel blocker and either dofetilide or amiodarone can maintain anti-AF properties, while the risk of ventricular arrhythmias is reduced.

U2 - 10.1007/s00424-016-1883-9

DO - 10.1007/s00424-016-1883-9

M3 - Journal article

VL - 468

SP - 1853

EP - 1863

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

SN - 0031-6768

IS - 11

ER -

ID: 167219222