title: Intrapericardial ranolazine prolongs atrial refractory period and markedly reduces atrial fibrillation inducibility in the intact porcine heart.
abstract: BACKGROUND
  Extensive experimental studies and clinical evidence (Metabolic Efficiency with Ranzolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction-36 [MERLIN TIMI-36] trial) indicate potential antiarrhythmic efficacy of the antianginal agent ranolazine. Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized.
  
  
  RESULTS
  The effects of intrapericardial (IPC) administration of ranolazine (50-mg bolus) on right atrial and right ventricular effective refractory periods (ERP), atrial fibrillation threshold, and ventricular fibrillation threshold were determined in 17 closed-chest anesthetized pigs. IPC ranolazine increased atrial ERP in a time-dependent manner from 129 +/- 5.14 to 186 +/- 9.78 ms (P < 0.01, N = 7) but did not significantly affect ventricular ERP (from 188.3 +/- 4.6 to 201 +/- 4.3 ms (NS, N = 6). IPC ranolazine increased atrial fibrillation threshold from 4.8 +/- 0.8 to 28 +/- 2.3 mA (P < 0.03, N = 6) and ventricular fibrillation threshold (from 24 +/- 3.56 baseline to 29.33 +/- 2.04 mA at 10-20 minutes, P < 0.03, N = 6). No significant change in mean arterial pressure was observed (from 92.8 +/- 7.1 to 74.8 +/- 7.5 mm Hg, P < 0.125, N = 5, at 7 minutes).
  
  
  CONCLUSIONS
  IPC ranolazine exhibits striking atrial antiarrhythmic actions as evidenced by increases in refractoriness and in fibrillation inducibility without significantly altering mean arterial blood pressure. Ranolazine's effects on the atria appear to be more potent than those on the ventricles.
authors.affiliation: University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Carvas
authors.forename: Bruno C G
authors.initials: BC
authors.lastname: Nascimento
authors.forename: Mariana
authors.initials: M
authors.lastname: Acar
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007267:Injections; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D000069458:Ranolazine; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D000069458:Ranolazine