Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart.
BACKGROUND
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.


RESULTS
In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (approximately 9 microM 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.
Kumar
Kapil
K
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nearing
Bruce D
BD
Carvas
Marcelo
M
Nascimento
Bruno C G
BC
Acar
Mariana
M
Belardinelli
Luiz
L
Verrier
Richard L
RL
D000083:Acetanilides / Q000008:administration & dosage / Q000494:pharmacology*; D000109:Acetylcholine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D000069458:Ranolazine; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013552:Swine; D013997:Time Factors
D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D000069458:Ranolazine; D000109:Acetylcholine