{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:26:30Z","timestamp":1791264390511,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009918","name":"Oda og Hans Svenningsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009918","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007505","name":"Kirsten og Freddy Johansens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Inhibition of the G\u2010protein gated ACh\u2010activated inward rectifier potassium current, <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti\u2010arrhythmic and electrophysiological properties of a novel putatively potent and highly specific <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> inhibitor, XAF\u20101407 (3\u2010methyl\u20101\u2010[5\u2010phenyl\u20104\u2010[4\u2010(2\u2010pyrrolidin\u20101\u2010ylethoxymethyl)\u20101\u2010piperidyl]thieno[2,3\u2010d]pyrimidin\u20106\u2010yl]azetidin\u20103\u2010ol), were characterised for the first time in vitro and investigated in horses with persistent AF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The pharmacological ion channel profile of XAF\u20101407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self\u2010sustained AF. The electrophysiological effects of XAF\u20101407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug\u2010induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>XAF\u20101407 potently and selectively inhibited K<jats:sub>ir<\/jats:sub>3.1\/3.4 and K<jats:sub>ir<\/jats:sub>3.4\/3.4, underlying the <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> current. XAF\u20101407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF\u20101407 shortened atrioventricular\u2010nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>XAF\u20101407 efficiently cardioverted sustained tachypacing\u2010induced AF of short duration in horses without notable side effects. This supports <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15100","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T02:30:00Z","timestamp":1590028200000},"page":"3778-3794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effect of selective <i>I<\/i><sub>K,ACh<\/sub> inhibition by XAF\u20101407 in an equine model of tachypacing\u2010induced persistent atrial fibrillation"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-7220","authenticated-orcid":false,"given":"Merle Friederike","family":"Fenner","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Carstensen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dalgas Nissen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Melis Hesselkilde","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Scott Lunddahl","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Adler Hess Jensen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameli Victoria","family":"Loft\u2010Andersen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Taastrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-8329","authenticated-orcid":false,"given":"Stefan Michael","family":"Sattler","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Medicine I University Hospital Munich, Campus Grosshadern, Ludwig\u2010Maximilians University Munich (LMU)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pyotr","family":"Platonov","sequence":"additional","affiliation":[{"name":"Arrhythmia Clinic, Sk\u00e5ne University Hospital and Department of Cardiology, Clinical Sciences Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"El\u2010Haou","sequence":"additional","affiliation":[{"name":"Xention Ltd.  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