Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

• Published in: Journal of cardiovascular electrophysiology Vol. 20; no. 7; pp. 796 - 802
• Main Authors: KUMAR, KAPIL, NEARING, BRUCE D., CARVAS, MARCELO, NASCIMENTO, BRUNO C.G., ACAR, MARIANA, BELARDINELLI, LUIZ, VERRIER, RICHARD L.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-07-2009
• Subjects: Acetanilides - administration & dosage; Acetanilides - pharmacology; Acetylcholine; Animals; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - pharmacology; atrial effective refractory period; atrial electrical properties; atrial fibrillation; Atrial Fibrillation - drug therapy; Atrial Fibrillation - etiology; Atrial Fibrillation - physiopathology; Cardiac Pacing, Artificial; Disease Models, Animal; Electrophysiologic Techniques, Cardiac; Female; Heart Atria - drug effects; Heart Atria - physiopathology; Heart Conduction System - drug effects; Heart Conduction System - physiopathology; Infusions, Intravenous; Male; Piperazines - administration & dosage; Piperazines - pharmacology; Ranolazine; Refractory Period, Electrophysiological - drug effects; Swine; Time Factors
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.2009.01437.x

Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI‐36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals.
Methods and Results: In 12 closed‐chest anesthetized pigs, effects of intravenous ranolazine (∼9 μM plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29–50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24–34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71–109) ms to 98 (86–121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811–1220) seconds to 621 (549–761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7–20.5) Hz to 7.6 (2.9–8.8) Hz (P = 0.02, n = 6).
Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency‐dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation.