Electrophysiological effects of ranolazine in a goat model of lone atrial fibrillation

D. Opacic, A. van Hunnik, S. Zeemering, A. Dhalla, L. Belardinelli, U. Schotten, S. Verheule*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)

Abstract

BACKGROUND There is still an unmet need for pharmacologic treatment of atrial fibrillation (AF) with few effects on ventricular electrophysiology. Ranolazine is an antiarrhythmic drug reported to have strong atrial selectivity.OBJECTIVE The purpose of this study was to investigate the electro-physiological effects of ranolazine in atria with AF-induced electrical remodeling in a model of lone AF in awake goats.METHODS Electrode patches were implanted on the atrial epicardium of 8 Dutch milk goats. Experiments were performed at baseline and after 2 and 14 days of electrically maintained AF. Several electro-physiological parameters and AF episode duration were measured during infusion of vehicle and different doses of ranolazine (target plasma levels 4, 8, and 16 mM, respectively).RESULTS The highest dose of ranolazine significantly prolonged atrial effective refractory period and decreased atrial conduction velocity at baseline and after 2 days of AF. After 2 weeks of AF, ranolazine prolonged the p5 and p50 of AF cycle length distribution in a dose-dependent manner but was not effective in restoring sinus rhythm. No adverse ventricular arrhythmic events (eg, premature ventricular beats or signs of hemodynamic instability) were observed during infusion of ranolazine at any point in the study.CONCLUSION The lowest investigated dose of ranolazine, which is expected to block both late I-Na and atrial peak I-Na, had no effect on the investigated electrophysiological parameters. The highest dose affected both atrial and ventricular electrophysiological parameters at different stages of AF-induced remodeling but was not efficacious in cardioverting AF to sinus rhythm in a goat model of lone AF.
Original languageEnglish
Pages (from-to)615-622
Number of pages8
JournalHeart Rhythm
Volume18
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021
Externally publishedYes

Keywords

  • Antiarrhythmic drugs
  • Atrial fibrillation
  • Goat
  • Ranolazine
  • Remodeling

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