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Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.
Abstract: 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. 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. 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.
© 2019 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.
Publication Date: 2019-01-28 PubMed ID: 30661267PubMed Central: PMC6849868DOI: 10.1111/jce.13849Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study is examining the effects of two antiarrhythmic drugs, dofetilide and ranolazine, on the atrial fibrillatory rate, a potential heart disease biomarker, in horses. This is achieved by monitoring changes following treatment on surface electrocardiography in an acute model of atrial fibrillation.
Study Design and Methodology
- The research was conducted on eight horses each subjected to pacing-induced atrial fibrillation (AF) on four separate days.
- The horses were treated with dofetilide, ranolazine, a combination of the two, or a saline control for comparison. These treatments were administered in four incremental doses.
- To understand the effects of the treatments, atrial fibrillatory activity was extracted from surface electrocardiographs (ECGs) using a process called spatiotemporal QRST cancellation.
Findings of the Study
- The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm.
- Dofetilide was found to reduce the atrial fibrillatory rate following the infusion of low doses and within 5 minutes preceding cardioversion. This result was statistically significant (P < 0.05).
- Ranolazine was seen to cause a reduction in the atrial fibrillatory rate in the last minute before cardiac conversion, another statistically significant result (P < 0.05).
- The combination of dofetilide and ranolazine reduced the atrial fibrillatory rate in a manner similar to dofetilide used alone.
- There was a trend towards a lower atrial fibrillatory rate before drug infusion among horses cardioverting on low doses of the drugs.%+}
Conclusions
- The atrial fibrillatory rate gathered from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine.
- Ranolazine and dofetilide had notably different effects, with dofetilide causing a reduction in the atrial fibrillatory rate and ranolazine demonstrating a cardioverting mechanism distinctly different from a slowing of the fibrillatory process.
Cite This Article
APA
Carstensen H, Hesselkilde EZ, Haugaard MM, Flethøj M, Carlson J, Pehrson S, Jespersen T, Platonov PG, Buhl R.
(2019).
Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.
J Cardiovasc Electrophysiol, 30(4), 596-606.
https://doi.org/10.1111/jce.13849 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
- Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Taastrup, Denmark.
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
- Arrhythmia Clinic, Skåne University Hospital, Lund, Sweden.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
MeSH Terms
- Action Potentials
- Animals
- Anti-Arrhythmia Agents / pharmacology
- Atrial Fibrillation / diagnosis
- Atrial Fibrillation / drug therapy
- Atrial Fibrillation / physiopathology
- Disease Models, Animal
- Drug Therapy, Combination
- Electrocardiography
- Female
- Heart Rate / drug effects
- Horses
- Male
- Phenethylamines / pharmacology
- Potassium Channel Blockers / pharmacology
- Ranolazine / pharmacology
- Sodium Channel Blockers / pharmacology
- Sulfonamides / pharmacology
- Time Factors
Grant Funding
- DFF-1331-00313B / The Danish Council for Independent Research
- 20140734 / The Swedish Heart-Lung Foundation
- Not available / The Danish Horse Levy Foundation
References
This article includes 29 references
- Zimetbaum P. Antiarrhythmic drug therapy for atrial fibrillation.. Circulation 2012;125:381‐389.
- Reiffel JA, Camm AJ, Belardinelli L. The HARMONY Trial: combined ranolazine and dronedarone in the management of paroxysmal atrial fibrillation: mechanistic and therapeutic synergism.. Circ Arrhythm Electrophysiol 2015;8:1048‐1056.
- Carstensen H, Kjær L, Haugaard MM. Antiarrhythmic effects of combining dofetilide and ranolazine in a model of acutely induced atrial fibrillation in horses.. J Cardiovasc Pharmacol 2018;71:26‐35.
- Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine.. Heart Rhythm 2011;8:1281‐1290.
- Antzelevitch C, Belardinelli L, Wu L. Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent.. J Cardiovasc Pharmacol Ther 2004;9(suppl 1):S65‐S83.
- Holm M, Pehrson S, Ingemansson M. Non‐invasive assessment of the atrial cycle length during atrial fibrillation in man: introducing, validating and illustrating a new ECG method.. Cardiovasc Res 1998;38:69‐81.
- Bollmann A, Kanuru N, McTeague K, Walter P, DeLurgio D, Langberg J. Frequency analysis of human atrial fibrillation using the surface electrocardiogram and its response to ibutilide.. Am J Cardiol 1998;81:1439‐1445.
- Stridh M, Sommo L. Spatiotemporal QRST cancellation techniques for analysis of atrial fibrillation.. IEEE Trans Biomed Eng 2001;48:105‐111.
- Aunes M, Egstrup K, Frison L. Rapid slowing of the atrial fibrillatory rate after administration of AZD7009 predicts conversion of atrial fibrillation.. J Electrocardiol 2014;47:316‐323.
- Husser D, Stridh M, Sornmo L. Time‐frequency analysis of the surface electrocardiogram for monitoring antiarrhythmic drug effects in atrial fibrillation.. Am J Cardiol 2005;95:526‐528.
- Niwano S, Sasaki T, Kurokawa S. Predicting the efficacy of antiarrhythmic agents for interrupting persistent atrial fibrillation according to spectral analysis of the fibrillation waves on the surface ECG.. Circ J 2009;73:1210‐1218.
- Aoyama Y, Niwano S, Niwano H. Repetitive evaluation of fibrillation cycle length predicts the efficacy of bepridil for interruption of long‐lasting persistent atrial fibrillation.. Int Heart J 2011;52:353‐358.
- Raygor VP, Ng J, Goldberger JJ. Surface ECG f wave analysis of dofetilide drug effect in the atrium.. J Cardiovasc Electrophysiol 2015;26:644‐648.
- Mochalina N, Juhlin T, Öhlin B, Carlson J, Holmqvist F, Platonov PG. Predictors of successful cardioversion with vernakalant in patients with recent‐onset atrial fibrillation.. Ann Noninvasive Electrocardiol 2015;20:140‐147.
- Black‐Maier EW, Pokorney SD, Barnett AS. Ranolazine reduces atrial fibrillatory wave frequency.. Europace 2017;19:1096‐1100.
- Reef VB, Bonagura J, Buhl R. Recommendations for management of equine athletes with cardiovascular abnormalities.. J Vet Intern Med 2014;28:749‐761.
- Haugaard MM, Pehrson S, Carstensen H. Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses.. J Vet Intern Med 2015;29:339‐347.
- Ohmura H, Nukada T, Mizuno Y, Yamaya Y, Nakayama T, Amada A. Safe and efficacious dosage of flecainide acetate for treating equine atrial fibrillation.. J Vet Med Sci 2000;62:711‐715.
- Haugaard MM, Hesselkilde EZ, Pehrson S. Pharmacologic inhibition of small‐conductance calcium‐activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses.. Heart Rhythm 2015;12:825‐835.
- Hesselkilde EZ, Carstensen H, Haugaard MM. Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation.. BMC Cardiovasc Disord 2017;17:289.
- Husser D, Stridh M, Cannom DS. Validation and clinical application of time‐frequency analysis of atrial fibrillation electrocardiograms.. J Cardiovasc Electrophysiol 2007;18:41‐46.
- Mounsey JP, DiMarco JP. Cardiovascular drugs. Dofetilide.. Circulation 2000;102:2665‐2670.
- Yang T, Chun YW, Stroud DM. Screening for acute IKr block is insufficient to detect torsades de pointes liability: role of late sodium current.. Circulation 2014;130:224‐234.
- Yoshida T, Niwano S, Inuo K. Evaluation of the effect of bepridil on paroxysmal atrial fibrillation: relationship between efficacy and the f‐f interval in surface ECG recordings.. Circ J 2003;67:11‐15.
- Wijffels MCEF, Dorland R, Mast F, Allessie MA. Widening of the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat: effects of cibenzoline, hydroquinidine, flecainide, and d‐sotalol.. Circulation 2000;102:260‐267.
- Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The “leading circle” concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle.. Circ Res 1977;41:9‐18.
- Choudhary MB, Holmqvist F, Carlson J, Nilsson HJ, Roijer A, Platonov PG. Low atrial fibrillatory rate is associated with spontaneous conversion of recent‐onset atrial fibrillation.. Europace 2013;15:1445‐1452.
- Fukaya H, Niwano S, Satoh D. Inhomogenic effect of bepridil on atrial electrical remodeling in a canine rapid atrial stimulation model.. Circ J 2008;72:318‐326.
- van Hunnik A, Lau DH, Zeemering S, Kuiper M, Verheule S, Schotten U. Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness.. Heart Rhythm 2016;13:964‐972.
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