title: Ranolazine terminates atrial flutter and fibrillation in a canine model.
abstract: BACKGROUND
  Ranolazine has been shown to have antiarrhythmic properties.
  
  
  OBJECTIVE
  We tested the hypothesis that intravenous ranolazine would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model.
  
  
  METHODS
  In 6 dogs with sterile pericarditis, we performed electrophysiological measurements of the atrial effective refractory period (AERP) and conduction time (CT) while pacing from the right atrial appendage, Bachmann bundle, and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms before and after the administration of ranolazine. In 13 induced episodes of AFL (n = 9) and AF (n = 4), ranolazine was administered intravenously as a 3.2 mg/kg bolus, followed by a maintenance infusion of 0.17 mg/(kg·min). Six episodes (4 AFL and 2 AF) were induced in the open-chest state to perform simultaneous, multisite (486 electrodes), epicardial mapping of the arrhythmia and its termination.
  
  
  RESULTS
  Ranolazine terminated 7 of 9 AFL and 3 of 4 AF episodes. Ranolazine significantly prolonged the AFL CL by a mean of 43 ms (P < .001) and the AF CL by a mean of 34 ms (P < .01). The AERP was prolonged (P < .05 overall), and the atrial capture threshold increased minimally (P < .01 for all). Ranolazine prolonged CTs (P < .01 overall). During open-chest, multisite mapping, block in the region of slow conduction in the reentrant circuit terminated AFL and interruption of the regular driver terminated AF.
  
  
  CONCLUSIONS
  Ranolazine terminated AFL/AF in our canine sterile pericarditis model by interrupting the regular driver. Ranolazine was found to significantly prolong the AERP, CT, and tachycardia CLs.
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio. Electronic address: ashish.bhimani@gmail.com.
authors: Ashish A
authors: AA
authors: Bhimani
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Tomoo
authors: T
authors: Yasuda
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Shervin A
authors: SA
authors: Sadrpour
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Celeen M
authors: CM
authors: Khrestian
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Seungyup
authors: S
authors: Lee
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Dewan
authors: D
authors: Zeng
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Luiz
authors: L
authors: Belardinelli
authors: Division of Cardiovascular Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Albert L
authors: AL
authors: Waldo
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D000818:Animals; D001145:Arrhythmias, Cardiac; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006329:Heart Conduction System / Q000002:abnormalities* / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D010879:Piperazines / Q000008:administration & dosage*; D000069458:Ranolazine; D026941:Sodium Channel Blockers; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D026941:Sodium Channel Blockers; D000069458:Ranolazine
keywords: Atrial fibrillation; Atrial flutter; Mapping; Ranolazine; Termination