{"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":1791264390158,"version":"4.1.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["675351"],"award-info":[{"award-number":["675351"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["CVON 2014-09 RACE V"],"award-info":[{"award-number":["CVON 2014-09 RACE V"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Aims:<\/jats:bold> The acetylcholine-activated inward rectifier potassium current (I<jats:sub>KACh<\/jats:sub>) has been proposed as an atrial-selective target for the treatment of atrial fibrillation (AF). Using a novel selective I<jats:sub>KACh<\/jats:sub> inhibitor XAF-1407, the study investigates the effect of I<jats:sub>KACh<\/jats:sub> inhibition in goats with pacing-induced, short-term AF.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Ten goats (57 \u00b1 5\u00a0kg) were instrumented with pericardial electrodes. Electrophysiological parameters were assessed at baseline and during intravenous infusion of XAF-1407 (0.3, 3.0\u00a0mg\/kg) in conscious animals before and after 2 days of electrically induced AF. Following a further 2 weeks of sustained AF, cardioversion was attempted with either XAF-1407 (0.3 followed by 3\u00a0mg\/kg) or with vernakalant (3.7 followed by 4.5\u00a0mg\/kg), an antiarrhythmic drug that inhibits the fast sodium current and several potassium currents. During a final open chest experiment, 249 unipolar electrograms were recorded on each atrium to construct activation patterns and AF cardioversion was attempted with XAF-1407.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> XAF-1407 prolonged atrial effective refractory period by 36\u00a0ms (45%) and 71\u00a0ms (87%) (0.3 and 3.0\u00a0mg\/kg, respectively; pacing cycle length 400\u00a0ms, 2 days of AF-induced remodeling) and showed higher cardioversion efficacy than vernakalant (8\/9 vs. 5\/9). XAF-1407 caused a minor decrease in the number of waves per AF cycle in the last seconds prior to cardioversion. Administration of XAF-1407 was associated with a modest increase in QTc (&amp;lt;10%). No ventricular proarrhythmic events were observed.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> XAF-1407 showed an antiarrhythmic effect in a goat model of AF. The study indicates that I<jats:sub>KACh<\/jats:sub> represents an interesting therapeutic target for treatment of AF. To assess the efficacy of XAF-1407 in later time points of AF-induced remodeling, follow-up studies with longer period of AF maintenance would be necessary.<\/jats:p>","DOI":"10.3389\/fphar.2020.608410","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T06:56:23Z","timestamp":1611730583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["The Acetylcholine-Activated Potassium Current Inhibitor XAF-1407 Terminates Persistent Atrial Fibrillation in Goats"],"prefix":"10.3389","volume":"11","author":[{"given":"Vladim\u00edr","family":"Sobota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"van Hunnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"van Tuijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Kuiper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Milnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jespersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schotten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Verheule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.yjmcc.2009.08.013","article-title":"Cardiac strong inward rectifier potassium channels","volume":"48","author":"Anumonwo","year":"2010","journal-title":"J. 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