Advanced

Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation

Carstensen, Helena; Hesselkilde, Eva Zander; Haugaard, Maria Mathilde; Flethøj, Mette; Carlson, Jonas LU ; Pehrson, Steen LU ; Jespersen, Thomas; Platonov, Pyotr G. LU and Buhl, Rikke (2019) In Journal of Cardiovascular Electrophysiology
Abstract

Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Methods and Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean... (More)

Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Methods and Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P < 0.05) and within 5 minutes preceding cardioversion (P < 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P < 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs. Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
atrial fibrillation, atrial fibrillatory rate, combination therapy, dofetilide, ranolazine
in
Journal of Cardiovascular Electrophysiology
publisher
Wiley-Blackwell
external identifiers
  • scopus:85060757926
ISSN
1045-3873
DOI
10.1111/jce.13849
language
English
LU publication?
yes
id
204d5aa1-7e53-4b24-8954-2dd539373660
date added to LUP
2019-02-13 09:08:49
date last changed
2019-03-05 04:32:55
@article{204d5aa1-7e53-4b24-8954-2dd539373660,
  abstract     = {<p>Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Methods and Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P &lt; 0.05) and within 5 minutes preceding cardioversion (P &lt; 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P &lt; 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs. Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.</p>},
  author       = {Carstensen, Helena and Hesselkilde, Eva Zander and Haugaard, Maria Mathilde and Flethøj, Mette and Carlson, Jonas and Pehrson, Steen and Jespersen, Thomas and Platonov, Pyotr G. and Buhl, Rikke},
  issn         = {1045-3873},
  keyword      = {atrial fibrillation,atrial fibrillatory rate,combination therapy,dofetilide,ranolazine},
  language     = {eng},
  month        = {01},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Cardiovascular Electrophysiology},
  title        = {Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation},
  url          = {http://dx.doi.org/10.1111/jce.13849},
  year         = {2019},
}