The antianginal agent ranolazine is a potent antiarrhythmic agent that reduces ventricular arrhythmias: through a mechanism favoring inhibition of late sodium channel

Cardiovascular Therapeutics
Robert A KlonerAnil Bhandari

Abstract

The antianginal agent ranolazine (R) has shown some promise as an antiarrhythmic agent but its mechanism of action is not known. Previously, we have shown that R suppresses ventricular arrhythmias at a concentration >10 μM that may affect multiple ion currents including IKr. The present study was carried out to determine the effects of low dose (4 μM) of R that primarily inhibits late I(Na) on ischemia/reperfusion induced ventricular arrhythmias. We subjected 20 anesthetized rats to 5 min of proximal left coronary artery occlusion followed by 5 min of reperfusion. Rats were randomized to vehicle control (C; n = 10) versus low dose R (n = 10; 3.33 mg/kg i.v. bolus plus 3.2 mg/kg/h R started 20 min prior to occlusion, which yields a concentration of 4 μM, within the known level that blocks late Na channels but well below the level that has effect on IKr or peak I(Na)). Reperfusion-induced arrhythmias were quantitated by electrocardiographic monitoring. In the C group 9/10 rats developed any arrhythmias versus 3/10 in the R group (P = 0.02); 6/10 developed ventricular tachycardia (VT) in the C group versus 0/10 in the R group (P = 0.01). The median number of episodes of VT were 1.5 in the C group versus 0 in the R group (P = 0.005...Continue Reading

References

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Aug 1, 2006·Journal of the American College of Cardiology·Peter H StoneUNKNOWN ERICA Investigators
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May 9, 2008·Journal of Molecular and Cellular Cardiology·Sharon L HaleRobert A Kloner
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Citations

Jan 8, 2013·Cardiovascular Drugs and Therapy·Carol Ann Remme, Arthur A M Wilde
Feb 5, 2013·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Peter MilbergLars Eckardt
Jun 6, 2014·Herzschrittmachertherapie & Elektrophysiologie·Anja SchadeThomas Deneke
Jul 18, 2015·Revista Española De Cardiología·Eva M Calderón-SánchezAntonio Ordóñez
Apr 7, 2017·Journal of Cardiovascular Pharmacology and Therapeutics·Laura A HundahlThomas Jespersen
Jun 28, 2019·Journal of Cardiovascular Pharmacology and Therapeutics·Vassileios MoschovidisIsaac Aidonidis
Nov 9, 2012·Journal of Cardiovascular Electrophysiology·Joan DowRobert A Kloner
Nov 10, 2013·Postgraduate Medicine·Robert A KlonerScarlett Geunes-Boyer
May 30, 2017·Circulation Journal : Official Journal of the Japanese Circulation Society·Takashi OgawaKaichiro Kamiya
Apr 17, 2018·Journal of Arrhythmia·George BazoukisCostas Tsioufis

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