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Published in: BMC Cardiovascular Disorders 1/2017

Open Access 01-12-2017 | Research article

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Authors: Eva Z. Hesselkilde, Helena Carstensen, Maria M. Haugaard, Jonas Carlson, Steen Pehrson, Thomas Jespersen, Rikke Buhl, Pyotr G. Platonov

Published in: BMC Cardiovascular Disorders | Issue 1/2017

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Abstract

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295 ± 52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269 ± 36 fpm in the control group (ns), and 364 ± 26 fpm in the horses with spontaneous persistent AF (P < 0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269 ± 36 fpm to a plateau of 313 ± 14 fpm before decreasing to 288 ± 28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P < 0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.
Literature
1.
go back to reference Holm M, Pehrson S, Ingemansson M, Sornmo L, Johansson R, Sandhall L, Sunemark M, Smideberg B, Olsson C, Olsson SB. 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(1):69–81.CrossRefPubMed Holm M, Pehrson S, Ingemansson M, Sornmo L, Johansson R, Sandhall L, Sunemark M, Smideberg B, Olsson C, Olsson SB. 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(1):69–81.CrossRefPubMed
2.
go back to reference Bollmann A, Kanuru NK, McTeague KK, Walter PF, DeLurgio DB, Langberg JJ. Frequency analysis of human atrial fibrillation using the surface electrocardiogram and its response to ibutilide. Am J Cardiol. 1998;81(12):1439–45.CrossRefPubMed Bollmann A, Kanuru NK, McTeague KK, Walter PF, DeLurgio DB, Langberg JJ. Frequency analysis of human atrial fibrillation using the surface electrocardiogram and its response to ibutilide. Am J Cardiol. 1998;81(12):1439–45.CrossRefPubMed
3.
go back to reference Haugaard MM, Pehrson S, Carstensen H, Flethoj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R. Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses. J Vet Intern Med. 2015;29(1):339–47.CrossRefPubMed Haugaard MM, Pehrson S, Carstensen H, Flethoj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R. Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses. J Vet Intern Med. 2015;29(1):339–47.CrossRefPubMed
4.
go back to reference Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethoj M, Praestegaard KF, Sorensen US, Diness JG, Grunnet M, Buhl R, et al. Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses. Heart Rhythm. 2015;12(4):825–35.CrossRefPubMed Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethoj M, Praestegaard KF, Sorensen US, Diness JG, Grunnet M, Buhl R, et al. Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses. Heart Rhythm. 2015;12(4):825–35.CrossRefPubMed
5.
go back to reference Else RW, Holmes JR. Pathological changes in atrial fibrillation in the horse. Equine Vet J. 1971;3(1):56–64.CrossRefPubMed Else RW, Holmes JR. Pathological changes in atrial fibrillation in the horse. Equine Vet J. 1971;3(1):56–64.CrossRefPubMed
6.
go back to reference Kirchhof P, Ammentorp B, Darius H, De Caterina R, Le Heuzey JY, Schilling RJ, Schmitt J, Zamorano JL. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European registry in atrial fibrillation (PREFER in AF). Europace. 2014;16(1):6–14.CrossRefPubMed Kirchhof P, Ammentorp B, Darius H, De Caterina R, Le Heuzey JY, Schilling RJ, Schmitt J, Zamorano JL. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European registry in atrial fibrillation (PREFER in AF). Europace. 2014;16(1):6–14.CrossRefPubMed
7.
go back to reference 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(7):711–5.CrossRefPubMed 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(7):711–5.CrossRefPubMed
8.
go back to reference van Loon G, Blissitt KJ, Keen JA, Young LE. Use of intravenous flecainide in horses with naturally-occurring atrial fibrillation. Equine Vet J. 2004;36(7):609–14.CrossRefPubMed van Loon G, Blissitt KJ, Keen JA, Young LE. Use of intravenous flecainide in horses with naturally-occurring atrial fibrillation. Equine Vet J. 2004;36(7):609–14.CrossRefPubMed
9.
go back to reference De Clercq D, van Loon G, Tavernier R, Duchateau L, Deprez P. Atrial and ventricular electrical and contractile remodeling and reverse remodeling owing to short-term pacing-induced atrial fibrillation in horses. J Vet Intern Med. 2008;22(6):1353–9.CrossRefPubMed De Clercq D, van Loon G, Tavernier R, Duchateau L, Deprez P. Atrial and ventricular electrical and contractile remodeling and reverse remodeling owing to short-term pacing-induced atrial fibrillation in horses. J Vet Intern Med. 2008;22(6):1353–9.CrossRefPubMed
10.
go back to reference Stridh M, Sornmo L, Spatiotemporal QRST. Cancellation techniques for analysis of atrial fibrillation. IEEE Trans Biomed Eng. 2001;48(1):105–11.CrossRefPubMed Stridh M, Sornmo L, Spatiotemporal QRST. Cancellation techniques for analysis of atrial fibrillation. IEEE Trans Biomed Eng. 2001;48(1):105–11.CrossRefPubMed
11.
go back to reference Platonov PG, Stridh M, de Melis M, Urban L, Carlson J, Corbucci G, Holmqvist F. Analysis of atrial fibrillatory rate during spontaneous episodes of atrial fibrillation in humans using implantable loop recorder electrocardiogram. J Electrocardiol. 2012;45(6):723–6.CrossRefPubMed Platonov PG, Stridh M, de Melis M, Urban L, Carlson J, Corbucci G, Holmqvist F. Analysis of atrial fibrillatory rate during spontaneous episodes of atrial fibrillation in humans using implantable loop recorder electrocardiogram. J Electrocardiol. 2012;45(6):723–6.CrossRefPubMed
12.
go back to reference 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(10):1445–52.CrossRefPubMed 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(10):1445–52.CrossRefPubMed
13.
go back to reference Husser D, Cannom DS, Bhandari AK, Stridh M, Sornmo L, Olsson SB, Bollmann A. Electrocardiographic characteristics of fibrillatory waves in new-onset atrial fibrillation. Europace. 2007;9(8):638–42.CrossRefPubMed Husser D, Cannom DS, Bhandari AK, Stridh M, Sornmo L, Olsson SB, Bollmann A. Electrocardiographic characteristics of fibrillatory waves in new-onset atrial fibrillation. Europace. 2007;9(8):638–42.CrossRefPubMed
14.
go back to reference Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92(7):1954–68.CrossRefPubMed Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92(7):1954–68.CrossRefPubMed
15.
go back to reference Bollmann A, Sonne K, Esperer HD, Toepffer I, Langberg JJ, Klein HU. Non-invasive assessment of fibrillatory activity in patients with paroxysmal and persistent atrial fibrillation using the Holter ECG. Cardiovasc Res. 1999;44(1):60–6.CrossRefPubMed Bollmann A, Sonne K, Esperer HD, Toepffer I, Langberg JJ, Klein HU. Non-invasive assessment of fibrillatory activity in patients with paroxysmal and persistent atrial fibrillation using the Holter ECG. Cardiovasc Res. 1999;44(1):60–6.CrossRefPubMed
16.
go back to reference Petrutiu S, Sahakian AV, Swiryn S. Short-term dynamics in fibrillatory wave characteristics at the onset of paroxysmal atrial fibrillation in humans. J Electrocardiol. 2007;40(2):155–60.CrossRefPubMed Petrutiu S, Sahakian AV, Swiryn S. Short-term dynamics in fibrillatory wave characteristics at the onset of paroxysmal atrial fibrillation in humans. J Electrocardiol. 2007;40(2):155–60.CrossRefPubMed
17.
go back to reference Fujiki A, Sakabe M, Nishida K, Mizumaki K, Inoue H. Role of fibrillation cycle length in spontaneous and drug-induced termination of human atrial fibrillation. Circ J. 2003;67(5):391–5.CrossRefPubMed Fujiki A, Sakabe M, Nishida K, Mizumaki K, Inoue H. Role of fibrillation cycle length in spontaneous and drug-induced termination of human atrial fibrillation. Circ J. 2003;67(5):391–5.CrossRefPubMed
18.
go back to reference Biffi M, Boriani G, Bronzetti G, Capucci A, Branzi A, Magnani B. Electrophysiological effects of flecainide and propafenone on atrial fibrillation cycle and relation with arrhythmia termination. Heart. 1999;82(2):176–82.CrossRefPubMedPubMedCentral Biffi M, Boriani G, Bronzetti G, Capucci A, Branzi A, Magnani B. Electrophysiological effects of flecainide and propafenone on atrial fibrillation cycle and relation with arrhythmia termination. Heart. 1999;82(2):176–82.CrossRefPubMedPubMedCentral
19.
go back to reference Bollmann A, Binias KH, Toepffer I, Molling J, Geller C, Klein HU. Importance of left atrial diameter and atrial fibrillatory frequency for conversion of persistent atrial fibrillation with oral flecainide. Am J Cardiol. 2002;90(9):1011–4.CrossRefPubMed Bollmann A, Binias KH, Toepffer I, Molling J, Geller C, Klein HU. Importance of left atrial diameter and atrial fibrillatory frequency for conversion of persistent atrial fibrillation with oral flecainide. Am J Cardiol. 2002;90(9):1011–4.CrossRefPubMed
20.
go back to reference Platonov PG, Corino VD, Seifert M, Holmqvist F, Sornmo L. Atrial fibrillatory rate in the clinical context: natural course and prediction of intervention outcome. Europace. 2014;16(Suppl 4) iv110-iv119 Platonov PG, Corino VD, Seifert M, Holmqvist F, Sornmo L. Atrial fibrillatory rate in the clinical context: natural course and prediction of intervention outcome. Europace. 2014;16(Suppl 4) iv110-iv119
Metadata
Title
Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation
Authors
Eva Z. Hesselkilde
Helena Carstensen
Maria M. Haugaard
Jonas Carlson
Steen Pehrson
Thomas Jespersen
Rikke Buhl
Pyotr G. Platonov
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2017
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-017-0720-1

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