{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:42:42Z","timestamp":1771461762983,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T00:00:00Z","timestamp":1404864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1002 - TP A03"],"award-info":[{"award-number":["SFB 1002 - TP A03"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2014,8]]},"abstract":"Abstract<\/jats:title>Purpose<\/jats:title>Torsades de pointes (T<\/jats:styled-content>dP<\/jats:styled-content>) tachycardias are triggered, polymorphic ventricular arrhythmias arising from early afterdepolarizations (EADs<\/jats:styled-content>) and increased dispersion of repolarization. Ranolazine is a new agent which reduces pathologically elevated late I<\/jats:italic>Na<\/jats:sub> but also I<\/jats:italic>Kr<\/jats:sub>. Aim of this study was to evaluate the effects of ranolazine in a validated isolated L<\/jats:styled-content>angendorff\u2010perfused rabbit heart model.<\/jats:p><\/jats:sec>Methods<\/jats:title>TdP was reproducibly induced with d\u2010sotalol (10\u22124<\/jats:sup>\u00a0mol\/L) and low potassium (K<\/jats:styled-content>) (1.0\u00a0mmol\/L for 5\u00a0min, pacing at CL<\/jats:styled-content> 1000\u00a0ms). In 10 hearts, ECG<\/jats:styled-content> and 8 epi\u2010 and endocardial monophasic action potentials were recorded. Action potential duration (APD<\/jats:styled-content>) was measured at 90% repolarization and dispersion defined as APD<\/jats:styled-content> max\u2013min.<\/jats:p><\/jats:sec>Results<\/jats:title>D\u2010sotalol prolonged APD<\/jats:styled-content>90<\/jats:sub> and increased dispersion of APD<\/jats:styled-content>90<\/jats:sub>, simultaneously causing EAD<\/jats:styled-content>s and induction of T<\/jats:styled-content>dP<\/jats:styled-content>. The combination of d\u2010sotalol and two concentrations of ranolazine did not increase dispersion of ventricular APD<\/jats:styled-content>90<\/jats:sub> as compared to vehicle. Ranolazine at 5\u00a0\u03bc<\/jats:italic>mol\/L did not cause additional induction of EAD<\/jats:styled-content>s and\/or T<\/jats:styled-content>dP but also did not significantly suppress arrhythmogenic triggers. The higher concentration of ranolazine (10\u00a0\u03bc<\/jats:italic>mol\/L) in combination with d\u2010sotalol caused further prolongation of APD<\/jats:styled-content>90<\/jats:sub>, at the same time reduction in APD<\/jats:styled-content>90<\/jats:sub> dispersion. In parallel, the incidence of EAD<\/jats:styled-content>s was reduced and an antitorsadogenic effect was seen.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>In the healthy isolated rabbit heart (where late I<\/jats:italic>Na<\/jats:sub> is not elevated), ranolazine does not cause proarrhythmia but exerts antiarrhythmic effects in a dose\u2010dependent manner against d\u2010sotalol\/low K<\/jats:styled-content>\u2010induced T<\/jats:styled-content>dP<\/jats:styled-content>. This finding\u2014despite additional APD<\/jats:styled-content> prolongation\u2014supports the safety of a combined use of both drugs and merits clinical investigation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12078","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T13:52:46Z","timestamp":1398865966000},"page":"170-177","source":"Crossref","is-referenced-by-count":14,"title":["Effects of Ranolazine on Torsades de Pointes Tachycardias in a Healthy Isolated Rabbit Heart Model"],"prefix":"10.1111","volume":"32","author":[{"given":"Samuel","family":"Sossalla","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Pneumologie\/Herzzentrum Georg\u2010August\u2010Universit\u00e4t G\u00f6ttingen G\u00f6ttingen Germany"},{"name":"DZHK (German Center for Cardiovascular Research) G\u00f6ttingen 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