Sossalla, Samuel and Wallisch, Nora and Toischer, Karl and Sohns, Christian and Vollmann, Dirk and Seegers, Joachim and Luethje, Lars and Maier, Lars S. and Zabel, Markus (2014) Effects of Ranolazine on Torsades de Pointes Tachycardias in a Healthy Isolated Rabbit Heart Model. CARDIOVASCULAR THERAPEUTICS, 32 (4). pp. 170-177. ISSN 1755-5914, 1755-5922
Full text not available from this repository. (Request a copy)Abstract
Purpose: Torsades de pointes (TdP) tachycardias are triggered, polymorphic ventricular arrhythmias arising from early afterdepolarizations (EADs) and increased dispersion of repolarization. Ranolazine is a new agent which reduces pathologically elevated late I-Na but also I-Kr. Aim of this study was to evaluate the effects of ranolazine in a validated isolated Langendorff-perfused rabbit heart model. Methods: TdP was reproducibly induced with d-sotalol (10(-4) mol/L) and low potassium (K) (1.0 mmol/L for 5 min, pacing at CL 1000 ms). In 10 hearts, ECG and 8 epi- and endocardial monophasic action potentials were recorded. Action potential duration (APD) was measured at 90% repolarization and dispersion defined as APD max-min. Results: D-sotalol prolonged APD(90) and increased dispersion of APD(90), simultaneously causing EADs and induction of TdP. The combination of d-sotalol and two concentrations of ranolazine did not increase dispersion of ventricular APD(90) as compared to vehicle. Ranolazine at 5 mu mol/L did not cause additional induction of EADs and/or TdP but also did not significantly suppress arrhythmogenic triggers. The higher concentration of ranolazine (10 mu mol/L) in combination with d-sotalol caused further prolongation of APD(90), at the same time reduction in APD(90) dispersion. In parallel, the incidence of EADs was reduced and an antitorsadogenic effect was seen. Conclusions: In the healthy isolated rabbit heart (where late INa is not elevated), ranolazine does not cause proarrhythmia but exerts antiarrhythmic effects in a dose-dependent manner against d-sotalol/low K-induced TdP. This finding-despite additional APD prolongation-supports the safety of a combined use of both drugs and merits clinical investigation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LATE SODIUM CURRENT; LATE NA+ CURRENT; VENTRICULAR REPOLARIZATION; ATRIAL-FIBRILLATION; EARLY AFTERDEPOLARIZATIONS; ANTIANGINAL AGENT; INHIBITION; MYOCYTES; DISPERSION; FAILURE; Action potential duration; Arrhythmias; Ranolazine; Sotalol; Torsades de Pointes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2019 06:58 |
| Last Modified: | 12 Sep 2019 06:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9837 |
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