{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T19:50:06Z","timestamp":1776282606136,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100005971","name":"German Heart Foundation","doi-asserted-by":"publisher","award":["F\/02\/14"],"award-info":[{"award-number":["F\/02\/14"]}],"id":[{"id":"10.13039\/501100005971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"crossref","award":["NHLBI R01-HL131461"],"award-info":[{"award-number":["NHLBI R01-HL131461"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hungarian National Research, Development, and Innovation Office","award":["NKFIH K-128851"],"award-info":[{"award-number":["NKFIH K-128851"]}]},{"name":"European Research Council under the European Union\u2019s Horizon 2020 research and innovation program","award":["850622"],"award-info":[{"award-number":["850622"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>Long 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We 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\u20135 (loss of IKr and reduction of IKs) rabbits. In vivo ECGs were recorded at baseline and after 10\u2009\u00b5M\/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 \u03b1- and \u03b2-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\u20135. Similarly, ex vivo, DHA shortened APD75 in WT and normalized it in LQT2, and additionally decreased AP triangulation in LQT2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Docosahexaenoic 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 \u03b1- or \u03b2-subunits to IKs are functionally impaired. Docosahexaenoic acid could represent a new genotype-specific therapy in LQT2.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euab228","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T19:12:05Z","timestamp":1628709125000},"page":"511-522","source":"Crossref","is-referenced-by-count":13,"title":["Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-8789","authenticated-orcid":false,"given":"Alessandro","family":"Castiglione","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Translational Cardiology, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland"},{"name":"Department of Translational Cardiology\/Electrophysiology, Institute of Physiology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tibor","family":"Hornyik","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Translational Cardiology, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland"},{"name":"Department of Translational Cardiology\/Electrophysiology, Institute of Physiology, University of Bern, Bern, Switzerland"},{"name":"Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg\u2014Bad Krozingen, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eike M","family":"W\u00fclfers","sequence":"additional","affiliation":[{"name":"Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg\u2014Bad Krozingen, Medical Faculty, University of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucilla","family":"Giammarino","sequence":"additional","affiliation":[{"name":"Translational Cardiology, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland"},{"name":"Department of Translational Cardiology\/Electrophysiology, Institute of Physiology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iask","family":"Edler","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica J","family":"Jowais","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Miami, Miami, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Rieder","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Translational Cardiology, Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland"},{"name":"Department of Translational Cardiology\/Electrophysiology, Institute of Physiology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Perez-Feliz","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg\u2014Bad Krozingen, Medical Faculty, University of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gideon","family":"Koren","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular Research Center, Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"B\u0151sze","sequence":"additional","affiliation":[{"name":"Animal Biotechnology Department, NARIC Agricultural Biotechnology Institute, G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Varr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Zehender","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"},{"name":"Department of Cardiology and Medical Intensive Care, St. Josefskrankenhaus, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara I","family":"Liin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Peter","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Miami, Miami, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Baczk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6999-841X","authenticated-orcid":false,"given":"Katja E","family":"Odening","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, University Heart Center Freiburg, 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