Evidence map›Paper›PMID 34601592›Full record

ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2022

Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion.

Alessandro Castiglione, Tibor Hornyik, Eike M Wülfers, Lucilla Giammarino, Iask Edler, Jessica J Jowais, Marina Rieder, Stefanie Perez-Feliz, Gideon Koren, Zsuzsanna Bősze and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in 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, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Functional Profiling ofCirculation. Genomic and precision medicine · 2025
    Article
  2. Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.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 · 2025
    Article
  3. Current and future precision therapy approaches in the long QT syndrome.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. 25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies.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 · 2023
    Review
  8. Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2.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 · 2023
    Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 5 countries.

Alessandro CastiglioneDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-5380-8789
Tibor HornyikDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Eike M WülfersInstitute of Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Faculty, University of Freiburg, Freiburg, Germany.
Lucilla GiammarinoTranslational Cardiology, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland.
Iask EdlerDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Jessica J JowaisDepartment of Physiology and Biophysics, University of Miami, Miami, FL, USA.
Marina RiederDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Stefanie Perez-FelizDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Gideon KorenDivision of Cardiology, Cardiovascular Research Center, Brown University, Providence, RI, USA.
Zsuzsanna BőszeAnimal Biotechnology Department, NARIC Agricultural Biotechnology Institute, Gödöllő, Hungary.
András VarróDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Manfred ZehenderDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Michael BrunnerDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Christoph BodeDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
Sara I LiinDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Hans Peter LarssonDepartment of Physiology and Biophysics, University of Miami, Miami, FL, USA.
István BaczkóDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Katja E OdeningDepartment of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID 0000-0001-6999-841X
University of Bern · CHUniversity of Freiburg · DELinköping University · SEUniversity of Miami · USUniversity of Szeged · HUAgricultural Biotechnology Institute · HUBrown University · US

Funding

Polyunsaturated fatty acids as anti-arrhythmic agents.R01HL131461 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BARRO-SORIA, RENE, DYKXHOORN, DEREK MICHAEL · 2016 to 2024
$5.1M
NHLBI NIH HHS R01 HL131461
6 · The paper itself

Abstract

aimLong QT syndrome (LQTS) is a cardiac channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Since current therapies often fail to prevent arrhythmic events in certain LQTS subtypes, new therapeutic strategies are needed. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, which enhances the repolarizing IKs current. METHODS AND

resultsWe investigated the effects of DHA in wild type (WT) and transgenic long QT Type 1 (LQT1; loss of IKs), LQT2 (loss of IKr), LQT5 (reduction of IKs), and LQT2-5 (loss of IKr and reduction of IKs) rabbits. In vivo ECGs were recorded at baseline and after 10 µM/kg DHA to assess changes in heart-rate corrected QT (QTc) and short-term variability of QT (STVQT). Ex vivo monophasic action potentials were recorded in Langendorff-perfused rabbit hearts, and action potential duration (APD75) and triangulation were assessed. Docosahexaenoic acid significantly shortened QTc in vivo only in WT and LQT2 rabbits, in which both α- and β-subunits of IKs-conducting channels are functionally intact. In LQT2, this led to a normalization of QTc and of its short-term variability. Docosahexaenoic acid had no effect on QTc in LQT1, LQT5, and LQT2-5. Similarly, ex vivo, DHA shortened APD75 in WT and normalized it in LQT2, and additionally decreased AP triangulation in LQT2.

conclusionsDocosahexaenoic acid exerts a genotype-specific beneficial shortening/normalizing effect on QTc and APD75 and reduces pro-arrhythmia markers STVQT and AP triangulation through activation of IKs in LQT2 rabbits but has no effects if either α- or β-subunits to IKs are functionally impaired. Docosahexaenoic acid could represent a new genotype-specific therapy in LQT2.

Indexed as

Docosahexaenoic AcidsLong QT SyndromeAnimalsAnimals, Genetically ModifiedArrhythmias, CardiacElectrocardiographyGenotypeHumansRabbitsDocosahexaenoic AcidsAction potential durationDocosahexaenoic acidGenotype-specific therapyIon currentsLong QT syndromeQT normalizationRabbit modelsRepolarization

Identifiers

PMID34601592
PMCPMC9125797
OpenAlexW3203225772

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.