Ranolazine and Vernakalant Prevent Ventricular Arrhythmias in an Experimental Whole-Heart Model of Short QT Syndrome.

FROMMEYER, GERRIT; ELLERMANN, CHRISTIAN; DECHERING, DIRK G.; KOCHHÄUSER, SIMON; BÖGEHOLZ, NILS; GÜNER, FATIH; LEITZ, PATRICK; POTT, CHRISTIAN; ECKARDT, LARS

Ranolazine and Vernakalant in Short QT Syndrome Background Ranolazine has been reported to have an antiarrhythmic potential. The aim of this study was to assess the electrophysiologic effects of ranolazine and to compare its effects to vernakalant in an experimental whole-heart model of short-QT syndrome. Methods Rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IKATP channel opener, was administered (1 μM). Results Endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (− 34 milliseconds, P 90; − 31 milliseconds, P 90 ( 18 milliseconds, P < 0.05) and ERP ( 28 milliseconds, P < 0.05) as compared with sole pinacidil treatment. Similar results were observed under the influence of vernakalant (APD90: 25 milliseconds, QT-interval: 34 milliseconds, ERP: 31 milliseconds). Under the influence of pinacidil, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and aggressive burst stimulation in 8 of 12 hearts (ranolazine group, 34 episodes) and 7 of 14 hearts (vernakalant group, 24 episodes). Additional infusion of ranolazine (1 of 12 hearts, 1 episode) or vernakalant (1 of 14 hearts, 3 episodes) led to a significant suppression of VF. Conclusion In the present pharmacologic model of short QT syndrome treatment with pinacidil led to an increased inducibility of VF in association with a reduction in ERP. Additional treatment with ranolazine or vernakalant reversed this effect and demonstrated potent antiarrhythmic properties based on an increase of ERP.

VENTRICULAR arrhythmia; ACTION potentials; ANALYTICAL biochemistry; ANIMAL experimentation; BIOLOGICAL models; COLLECTION & preservation of biological specimens; CHI-squared test; ELECTROCARDIOGRAPHY; FISHER exact test; HEART; PIPERAZINE; PROBABILITY theory; RABBITS; RESEARCH funding; STATISTICS; T-test (Statistics); DATA analysis; DATA analysis software; DESCRIPTIVE statistics; SHORT QT syndrome; PHARMACODYNAMICS; PREVENTION

Journal of Cardiovascular Electrophysiology, 2016, Vol 27, Issue 10, p1214

1045-3873

Academic Journal

10.1111/jce.13029