{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:55:39Z","timestamp":1768560939135,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T00:00:00Z","timestamp":1516579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010578","name":"German Cardiac Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010578","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hans and Gertie Fischer-Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>A significant antiarrhythmic potential of ryanodine receptor inhibition was reported in experimental studies. The aim of the present study was to assess potential antiarrhythmic effects of dantrolene in an experimental whole\u2010heart model of drug\u2010induced long\u2010QT syndrome (LQTS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 12 isolated rabbit hearts, long\u2010QT\u20102\u2010syndrome was simulated by infusion of erythromycin (300 \u03bcM). Twelve rabbit hearts were treated with veratridine (0.5 \u03bcM) to mimic long\u2010QT\u20103\u2010syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Monophasic action potentials and ECG showed a significant prolongation of QT\u2010interval (+71\u00a0ms, P\u00a0&lt;\u00a00.01) and action potential duration (APD, +43\u00a0ms, P\u00a0&lt;\u00a00.01) after infusion of erythromycin as compared with baseline. Similar results were obtained in veratridine\u2010treated hearts (QT\u2010interval: +43\u00a0ms, P\u00a0&lt;\u00a00.01; APD: +36\u00a0ms, P\u00a0&lt;\u00a00.01). Both erythromycin (+36\u00a0ms, P\u00a0&lt;\u00a00.05) and veratridine (+38\u00a0ms) significantly increased dispersion of repolarization.<\/jats:p><jats:p>Additional infusion of dantrolene (20 \u03bcM) did not significantly alter QT\u2010interval and APD but resulted in a significant reduction of dispersion of repolarization (erythromycin group: \u201333\u00a0ms, P\u00a0&lt;\u00a00.05; veratridine group: \u201329\u00a0ms, P\u00a0&lt;\u00a00.05).<\/jats:p><jats:p>Lowering of potassium concentration resulted in the occurrence of early afterdepolarizations (EAD) and polymorphic ventricular tachycardia (VT) in 9 of 12 erythromycin\u2010treated hearts (175 episodes) and 8 of 12 veratridine\u2010treated hearts (66 episodes). Additional infusion of dantrolene significantly reduced occurrence of polymorphic VT and resulted in occurrence of EAD and polymorphic VT in 1 of 12 erythromycin\u2010treated hearts (18 episodes) and 1 of 12 veratridine\u2010treated hearts (3 episodes).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Inhibition of the ryanodine receptor by dantrolene significantly reduced occurrence of polymorphic VT in drug\u2010induced LQTS. A significant reduction of spatial dispersion of repolarization represents a major antiarrhythmic mechanism. These results imply that dantrolene may represent a promising antiarrhythmic option in drug\u2010induced LQTS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.13412","type":"journal-article","created":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T12:26:19Z","timestamp":1515068779000},"page":"471-476","source":"Crossref","is-referenced-by-count":6,"title":["Ryanodine\u2010receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in an <i>ex vivo<\/i> model of long\u2010QT syndrome"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1431-9886","authenticated-orcid":false,"given":"Gerrit","family":"Frommeyer","sequence":"first","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Ellermann","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"B\u00f6geholz","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Kochh\u00e4user","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-9838","authenticated-orcid":false,"given":"Dirk G.","family":"Dechering","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fehr","sequence":"additional","affiliation":[{"name":"Clinic of Exotic Pets, Reptiles, Exotic and Feral Birds University of Hanover  Hanover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Division of Electrophysiology, Department of Cardiovascular Medicine University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.040403.114521"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2004.01.015"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62834"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.305146"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041336"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.007657"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.01.065"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100194"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.06.017"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2011.11.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr107"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.08.029"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2011.03.058"},{"key":"e_1_2_6_15_1","first-page":"100","article-title":"Drug\u2010induced 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