title: The Selective Late Sodium Current Inhibitor Eleclazine, Unlike Amiodarone, Does Not Alter Defibrillation Threshold or Dominant Frequency of Ventricular Fibrillation.
abstract: BACKGROUND
  We examined the effects of the selective late INa inhibitor eleclazine on the 50% probability of successful defibrillation (DFT50) before and after administration of amiodarone to determine its suitability for use in patients with implantable cardioverter defibrillators (ICDs).
  
  
  RESULTS
  In 20 anesthetized pigs, transvenous active-fixation cardiac defibrillation leads were fluoroscopically positioned into right ventricular apex through jugular vein. ICDs were implanted subcutaneously. Dominant frequency of ventricular fibrillation was analyzed by fast Fourier transform. The measurements were made before drug administration (control), and at 40 minutes after vehicle, eleclazine (2 mg/kg, i.v., bolus over 15 minutes), or subsequent/single amiodarone administration (10 mg/kg, i.v., bolus over 10 minutes). Eleclazine did not alter DFT50, dominant frequency, heart rate, or mean arterial pressure (MAP). Subsequent amiodarone increased DFT50 (P = 0.006), decreased dominant frequency (P = 0.022), and reduced heart rate (P = 0.031) with no change in MAP. Amiodarone alone increased DFT50 (P = 0.005; NS compared to following eleclazine) and decreased dominant frequency (P = 0.003; NS compared to following eleclazine).
  
  
  CONCLUSIONS
  Selective late INa inhibition with eleclazine does not alter DFT50 or dominant frequency of ventricular fibrillation when administered alone or in combination with amiodarone. Accordingly, eleclazine would not be anticipated to affect the margin of defibrillation safety in patients with ICDs.
authors.affiliation: *Beth Israel Deaconess Medical Center, Boston, MA; †Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; ‡Harvard Medical School, Boston, MA; and §Gilead Sciences, Inc, Foster City, CA.
authors.forename: Ana F G
authors.initials: AF
authors.lastname: Silva
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bonatti
authors.forename: Julio A P
authors.initials: JA
authors.lastname: Batatinha
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.forename: Dewan
authors.initials: D
authors.lastname: Zeng
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000638:Amiodarone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004554:Electric Countershock / Q000379:methods*; D008297:Male; D010077:Oxazepines / Q000494:pharmacology / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy; D061566:Voltage-Gated Sodium Channels / Q000502:physiology
chemical_list: D010077:Oxazepines; D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; C000624281:eleclazine; D000638:Amiodarone