New Insights into the Beneficial Electrophysiologic Profile of Ranolazine in Heart Failure: Prevention of Ventricular Fibrillation With Increased Postrepolarization Refractoriness and Without Drug-Induced Proarrhythmia

Abstract Background Ranolazine inhibits late Na+ and K+ currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF). Methods and R...

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Bibliographic Details
Published in:Journal of cardiac failure 2012-12, Vol.18 (12), p.939-949
Main Authors: Frommeyer, Gerrit, MD, Rajamani, Sridharan, PhD, Grundmann, Fabian, MD, Stypmann, Jörg, MD, Osada, Nani, PhD, Breithardt, Günter, MD, EFESC, FACC, FHRS, Belardinelli, Luiz, MD, Eckardt, Lars, MD, Milberg, Peter, MD
Format: Article
Language:English
Subjects:
Acetanilides - pharmacology
action potential prolongation
Action Potentials - drug effects
Animals
Anti-Arrhythmia Agents - pharmacology
Cardiovascular
Chronic heart failure
Disease Models, Animal
drug-induced proarrhythmia
Electrocardiography
Heart Failure - drug therapy
Piperazines - pharmacology
postrepolarization refractoriness
Rabbits
Ranolazine
Refractory Period, Electrophysiological - drug effects
Sotalol - pharmacology
Ventricular Fibrillation - prevention & control
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Summary:Abstract Background Ranolazine inhibits late Na+ and K+ currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF). Methods and Results In 12 female rabbits, CHF was induced by 4 weeks of rapid ventricular pacing leading to a decrease in ejection fraction. Twelve rabbits underwent sham operation. Isolated hearts were Langendorff perfused and demonstrated a significant QT prolongation after induction of heart failure. Ranolazine caused a concentration-dependent (10 and 30 μmol/L) increase of action potential duration (APD90 ) in sham-operated and failing hearts. Eight endo- and epicardial monophasic action potentials revealed a nonsignificant increase in spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period, resulting in a significant increase in postrepolarization refractoriness in sham-operated (+29 ms and +55 ms; P  
ISSN:1071-9164
1532-8414
DOI:10.1016/j.cardfail.2012.10.017