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 Cardiology2025
Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.
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, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Mechano-electrical feedback in transgenic rabbit models of long QT syndrome Type 2 and short QT syndrome Type 1.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 · 2026Article
- A rabbit is not a mouse: a framework for the initial welfare assessment and long-term monitoring of genetically altered laboratory rabbits.Frontiers in veterinary science · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
aimsLoss-of-function mutations in KCNQ1 and KCNH2 (α-subunits of the slow delayed IKs and rapid delayed IKr-conducting repolarising K+ channels) lead to long QT syndrome type 1 (LQT1) and 2 (LQT2), respectively. These channelopathies present with longer action potential duration (APD) and prolonged QT interval on electrocardiogram, which can ultimately lead to deadly arrhythmias. Here, we investigated the therapeutic potential of the polyunsaturated fatty acid docosahexaenoyl glycine (DHA-gly) in normalizing APD and QT interval in LQT2 by increasing IKs. METHODS AND
resultsThe effects of DHA-gly on electrical and mechanical parameters were assessed in Xenopus laevis oocytes, wild-type (WT), LQT1 (KCNQ1-Y315S), and LQT2 (KCNH2-G628S) transgenic rabbit models and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). DHA-gly increased IKs in oocytes and WT ventricular cardiomyocytes (VCMs) in a dose-dependent manner. Consequently, DHA-gly shortened APD in vitro and QT interval ex vivo in WT and LQT2 rabbits, but not in LQT1. However, DHA-gly was unable to reduce arrhythmia formation in LQT2. Beneficial APD/QT shortening effects were accompanied by a detrimental decrease in both cellular and ventricular contraction across all genotypes, including LQT1, which could be due to a shortening in Ca2+ transient duration observed in VCMs and hiPSC-CMs.
conclusionDHA-gly-induced IKs enhancement shows promising results in shortening APD/QT in LQT2 rabbits, while having no effect on LQT1 (impaired IKs). However, its adverse effect on cardiac contractility, even in LQT1, makes it unsuitable to treat LQTS patients. Our study highlights the importance of considering both electrical and mechanical effects of potential therapeutic compounds prior to clinical translation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.