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The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation

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The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation. / Wettwer, Erich; Christ, Torsten; Endig, Sebastian; Rozmaritsa, Nadiia; Matschke, Klaus; Lynch, Joseph J; Pourrier, Marc; Gibson, John K; Fedida, David; Knaut, Michael; Ravens, Ursula.

In: CARDIOVASC RES, Vol. 98, No. 1, 01.04.2013, p. 145-54.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wettwer, E, Christ, T, Endig, S, Rozmaritsa, N, Matschke, K, Lynch, JJ, Pourrier, M, Gibson, JK, Fedida, D, Knaut, M & Ravens, U 2013, 'The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation', CARDIOVASC RES, vol. 98, no. 1, pp. 145-54. https://doi.org/10.1093/cvr/cvt006

APA

Wettwer, E., Christ, T., Endig, S., Rozmaritsa, N., Matschke, K., Lynch, J. J., Pourrier, M., Gibson, J. K., Fedida, D., Knaut, M., & Ravens, U. (2013). The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation. CARDIOVASC RES, 98(1), 145-54. https://doi.org/10.1093/cvr/cvt006

Vancouver

Wettwer E, Christ T, Endig S, Rozmaritsa N, Matschke K, Lynch JJ et al. The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation. CARDIOVASC RES. 2013 Apr 1;98(1):145-54. https://doi.org/10.1093/cvr/cvt006

Bibtex

@article{d02c6bba9e954ee1b3d0d9b06d4b2dc4,
title = "The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation",
abstract = "AIMS: Vernakalant is a newly developed antiarrhythmic drug against atrial fibrillation (AF). However, its electrophysiological actions on human myocardium are unknown.METHODS AND RESULTS: Action potentials (APs) and ion currents were recorded in right atrial trabeculae and cardiomyocytes from patients in sinus rhythm (SR) and chronic AF. Vernakalant prolonged early repolarization in SR and AF, but late only in AF. AP amplitude (APA) and dV/dtmax were reduced in a concentration- and frequency-dependent manner with IC50 < 10 µM at >3 Hz. Effective refractory period was increased more than action potential duration (APD) in SR and AF. INa was blocked with IC50s of 95 and 84 µM for SR and AF, respectively (0.5 Hz). Vernakalant did not reduce outward potassium currents compared with time-matched controls. However, area under the current-time curve was reduced due to acceleration of current decline with IC50s of 19 and 12 µM for SR and AF, respectively. Vernakalant had less effect on APD than the IKr blocker E-4031, blocked IK,ACh, and had a small inhibitory effect on IK1 at 30 µM. L-Type Ca(2+) currents (SR) were reduced with IC50 of 84 µM.CONCLUSION: Rate-dependent block of Na(+) channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and IK,ACh could also contribute.",
keywords = "Action Potentials, Aged, Anisoles, Anti-Arrhythmia Agents, Arrhythmia, Sinus, Atrial Fibrillation, Calcium Channels, Chronic Disease, Female, Heart Atria, Humans, Male, Middle Aged, Myocytes, Cardiac, Potassium Channels, Pyrrolidines, Sodium Channels",
author = "Erich Wettwer and Torsten Christ and Sebastian Endig and Nadiia Rozmaritsa and Klaus Matschke and Lynch, {Joseph J} and Marc Pourrier and Gibson, {John K} and David Fedida and Michael Knaut and Ursula Ravens",
note = "Christ f{\"u}r: Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Pharmacol & Toxicol, D-01307 Dresden, Germany",
year = "2013",
month = apr,
day = "1",
doi = "10.1093/cvr/cvt006",
language = "English",
volume = "98",
pages = "145--54",
journal = "CARDIOVASC RES",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation

AU - Wettwer, Erich

AU - Christ, Torsten

AU - Endig, Sebastian

AU - Rozmaritsa, Nadiia

AU - Matschke, Klaus

AU - Lynch, Joseph J

AU - Pourrier, Marc

AU - Gibson, John K

AU - Fedida, David

AU - Knaut, Michael

AU - Ravens, Ursula

N1 - Christ für: Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Pharmacol & Toxicol, D-01307 Dresden, Germany

PY - 2013/4/1

Y1 - 2013/4/1

N2 - AIMS: Vernakalant is a newly developed antiarrhythmic drug against atrial fibrillation (AF). However, its electrophysiological actions on human myocardium are unknown.METHODS AND RESULTS: Action potentials (APs) and ion currents were recorded in right atrial trabeculae and cardiomyocytes from patients in sinus rhythm (SR) and chronic AF. Vernakalant prolonged early repolarization in SR and AF, but late only in AF. AP amplitude (APA) and dV/dtmax were reduced in a concentration- and frequency-dependent manner with IC50 < 10 µM at >3 Hz. Effective refractory period was increased more than action potential duration (APD) in SR and AF. INa was blocked with IC50s of 95 and 84 µM for SR and AF, respectively (0.5 Hz). Vernakalant did not reduce outward potassium currents compared with time-matched controls. However, area under the current-time curve was reduced due to acceleration of current decline with IC50s of 19 and 12 µM for SR and AF, respectively. Vernakalant had less effect on APD than the IKr blocker E-4031, blocked IK,ACh, and had a small inhibitory effect on IK1 at 30 µM. L-Type Ca(2+) currents (SR) were reduced with IC50 of 84 µM.CONCLUSION: Rate-dependent block of Na(+) channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and IK,ACh could also contribute.

AB - AIMS: Vernakalant is a newly developed antiarrhythmic drug against atrial fibrillation (AF). However, its electrophysiological actions on human myocardium are unknown.METHODS AND RESULTS: Action potentials (APs) and ion currents were recorded in right atrial trabeculae and cardiomyocytes from patients in sinus rhythm (SR) and chronic AF. Vernakalant prolonged early repolarization in SR and AF, but late only in AF. AP amplitude (APA) and dV/dtmax were reduced in a concentration- and frequency-dependent manner with IC50 < 10 µM at >3 Hz. Effective refractory period was increased more than action potential duration (APD) in SR and AF. INa was blocked with IC50s of 95 and 84 µM for SR and AF, respectively (0.5 Hz). Vernakalant did not reduce outward potassium currents compared with time-matched controls. However, area under the current-time curve was reduced due to acceleration of current decline with IC50s of 19 and 12 µM for SR and AF, respectively. Vernakalant had less effect on APD than the IKr blocker E-4031, blocked IK,ACh, and had a small inhibitory effect on IK1 at 30 µM. L-Type Ca(2+) currents (SR) were reduced with IC50 of 84 µM.CONCLUSION: Rate-dependent block of Na(+) channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and IK,ACh could also contribute.

KW - Action Potentials

KW - Aged

KW - Anisoles

KW - Anti-Arrhythmia Agents

KW - Arrhythmia, Sinus

KW - Atrial Fibrillation

KW - Calcium Channels

KW - Chronic Disease

KW - Female

KW - Heart Atria

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocytes, Cardiac

KW - Potassium Channels

KW - Pyrrolidines

KW - Sodium Channels

U2 - 10.1093/cvr/cvt006

DO - 10.1093/cvr/cvt006

M3 - SCORING: Journal article

C2 - 23341576

VL - 98

SP - 145

EP - 154

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 1

ER -