Evidence map›Paper›PMID 29018164›Full record

ArticleCirculation. Arrhythmia and electrophysiology2017

Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca

Jonas Goldin Diness, Lasse Skibsbye, Rafel Simó-Vicens, Joana Larupa Santos, Pia Lundegaard, Carlotta Citerni, Daniel Rafael Peter Sauter, Sofia Hammami Bomholtz, Jesper Hastrup Svendsen, Søren-Peter Olesen and 4 more

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In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it

0cells of the map it votes in

52citing papers in PubMed

6.1field-weighted citation impact, top 3% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 74 citations in OpenAlex.

Inhibition of the KNature medicine · 2024
Trial
First Clinical Study with AP30663 - a KClinical and translational science · 2020
Trial
Understanding the Diseased Atria.Physiology (Bethesda, Md.) · 2026
Review
Computational modelling of the pro- and antiarrhythmic effects of atrial high rate-dependent trafficking of small-conductance calcium-activated potassium channels.The Journal of physiology · 2026
Article
Prospective in silico trials identify combined SK and KThe Journal of physiology · 2026
Article
Conventional Antiarrhythmics Class I-IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias.Pharmaceuticals (Basel, Switzerland) · 2026
Review
NaInternational journal of cardiology. Heart & vasculature · 2025
Article
Cryo-EM structures of the small-conductance CaNature communications · 2025
Article
Activation of Small Conductance CaInternational journal of molecular sciences · 2025
Article
Evolution in electrophysiology 100 years after Einthoven: translational and computational innovations in rhythm control of atrial fibrillation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024
Review
Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024
Review
Therapeutic advances in atrial fibrillation based on animal models.Journal of Zhejiang University. Science. B · 2024
Review
From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.European cardiology · 2024
Review
Dual effects of the small-conductance CaAmerican journal of physiology. Heart and circulatory physiology · 2023
Article
Recent Advances in Antiarrhythmic Drug Therapy.Drugs · 2023
Review
Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
Review
Enhanced CaCirculation research · 2023
Article
Gating kinetics and pharmacological properties of small-conductance CaBiophysical journal · 2023
Article
Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events.Journal of cardiovascular electrophysiology · 2023
Article
Research on atrial fibrillation mechanisms and prediction of therapeutic prospects: focus on the autonomic nervous system upstream pathways.Frontiers in cardiovascular medicine · 2023
Review

4 · The record

Corrections and comments

Commented on by
Inhibition of Small-Conductance Ca2017

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Jonas Goldin DinessFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.). jgd@acesionpharma.com.

Lasse SkibsbyeFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Rafel Simó-VicensFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Joana Larupa SantosFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Pia LundegaardFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Carlotta CiterniFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Daniel Rafael Peter SauterFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Sofia Hammami BomholtzFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Jesper Hastrup SvendsenFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Søren-Peter OlesenFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Ulrik S SørensenFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Thomas JespersenFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Morten GrunnetFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Bo Hjorth BentzenFrom the Acesion Pharma, Copenhagen, Denmark (J.G.D., R.S.-V., C.C., D.R.P.S., S.H.B., U.S.S., M.G., B.H.B.); Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (L.S., J.L.S., P.L., D.R.P.S., S.-P.O., T.J., M.G., B.H.B.); and the Heart Centre, Rigshospitalet, Copenhagen, Denmark (J.H.S.).

Acesion Pharma (Denmark) · DK

Funding

Wellcome Trust 100406

6 · The paper itself

Abstract

backgroundEvidence has emerged that small-conductance Ca METHODS AND

resultsA 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.

conclusionsSK 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.

Indexed as

AcetamidesAnimalsAnisolesAtrial FibrillationCardiac Pacing, ArtificialDisease Models, AnimalDisease ProgressionPatch-Clamp TechniquesPyrrolidinesRefractory Period, ElectrophysiologicalSmall-Conductance Calcium-Activated Potassium ChannelsSwineAcetamidesAnisolesAP14145PyrrolidinesSmall-Conductance Calcium-Activated Potassium Channelsvernakalantatrial fibrillationblood pressureheart atriaswinevernakalant

Identifiers

PMID29018164

DOI10.1161/CIRCEP.117.005125

PMCPMC5647113

OpenAlexW2762661054

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.