The Selective Late Sodium Current Inhibitor Eleclazine, Unlike Amiodarone, Does Not Alter Defibrillation Threshold or Dominant Frequency of Ventricular Fibrillation.

Abstract

INTRODUCTION:

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).

METHODS AND 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).

CONCLUSION:

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: Ana F G Silva, Rodolfo Bonatti, Julio A P Batatinha, Bruce D Nearing, Dewan Zeng, Luiz Belardinelli, Richard L Verrier
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 69 Issue 3 Pg. 178-182 (Mar 2017) ISSN: 1533-4023 [Electronic] United States
• PMID: 28045761 (Publication Type: Journal Article)

Chemical References

• Oxazepines
• Sodium Channel Blockers
• Voltage-Gated Sodium Channels
• eleclazine
• Amiodarone

Topics

• Amiodarone (pharmacology, therapeutic use)
• Animals
• Electric Countershock (methods)
• Male
• Oxazepines (pharmacology, therapeutic use)
• Sodium Channel Blockers (pharmacology, therapeutic use)
• Swine
• Ventricular Fibrillation (drug therapy, physiopathology, therapy)
• Voltage-Gated Sodium Channels (physiology)