Skip to main content
SpringerLink
Log in

Mechanisms of Action of Antiarrhythmic Drugs in Atrial Fibrillation

  • Chapter
  • First Online:
Electrical Diseases of the Heart

  • 3163 Accesses

Abstract

The principal goal of antiarrhythmic therapy in the management of atrial fibrillation (AF) is to prolong the effective refractory period (ERP), which makes rapid activation of the atria impossible. Currently available antiarrhythmic drugs (AADs) prolong ERP by (1) prolonging the atrial action potential as in the case of delayed rectified potassium channel current (IKr) blockers such as d-sotalol, dofetilide, or ibutilide; (2) reducing excitability, thus promoting post-repolarization refractoriness (PRR), as in the case of sodium channel current (INa) blockers such as flecainide and propafenone, or (3) via both mechanism as in the case of multiple ion channels blockers such as amiodarone, dronedarone, ranolazine and vernakalant. The role of conduction slowing in anti-AF actions of INa blockers remains poorly understood. The present chapter describes our current understanding of anti-AF mechanisms of action of AADs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nattel S. New ideas about atrial fibrillation 50 years on. Nature. 2002;415:219–26.

    Article  PubMed  CAS  Google Scholar 

  2. Scherf D, Romano FJ, Terranova R. Experimental studies on auricular flutter and auricular fibrillation. Am Heart J. 1948;36:241–51.

    Article  PubMed  CAS  Google Scholar 

  3. Zhou S, Chang CM, Wu TJ, et al. Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation. Am J Physiol Heart Circ Physiol. 2002;283:H1244–52.

    PubMed  CAS  Google Scholar 

  4. Fenelon G, Shepard RK, Stambler BS. Focal origin of atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. J Cardiovasc Electro­physiol. 2003;14:1093–102.

    Article  PubMed  Google Scholar 

  5. Nitta T, Ishii Y, Miyagi Y, et al. Concurrent multiple left atrial focal activations with fibrillatory conduction and right atrial focal or reentrant activation as the mechanism in atrial fibrillation. J Thorac Cardiovasc Surg. 2004;127:770–8.

    Article  PubMed  Google Scholar 

  6. Gray RA, Pertsov AM, Jalife J. Incomplete reentry and epicardail breakthrough patterns during atrial fibrillation in the sheep heart. Circulation. 1996;94:­2649–61.

    Article  PubMed  CAS  Google Scholar 

  7. Valderrabano M, Chen PS, Lin SF. Spatial distribution of phase singularities in ventricular fibrillation. Circulation. 2003;108:354–9.

    Article  PubMed  Google Scholar 

  8. Nair K, Umapathy K, Farid T, et al. Intramural activation during early human ventricular fibrillation. Circ Arrhythm Electrophysiol. 2011;4:692–703.

    Article  PubMed  Google Scholar 

  9. Vaquero M, Calvo D, Jalife J. Cardiac fibrillation: from ion channels to rotors in the human heart. Heart Rhythm. 2008;5:872–9.

    Article  PubMed  Google Scholar 

  10. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954–68.

    Article  PubMed  CAS  Google Scholar 

  11. Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res. 2002;54:230–46.

    Article  PubMed  CAS  Google Scholar 

  12. Morillo CA, Klein GJ, Jones DL, Guiraudon CM. Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation. 1995;91:1588–95.

    Article  PubMed  CAS  Google Scholar 

  13. Iwasaki YK, Nishida K, Kato T, Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011;124:2264–74.

    Article  PubMed  CAS  Google Scholar 

  14. Verheule S, Wilson E, Everett T, et al. Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation. Circulation. 2003;107:2615–22.

    PubMed  Google Scholar 

  15. Li D, Melnyk P, Feng J, et al. Effects of experimental heart failure on atrial cellular and ionic electrophysiology. Circulation. 2000;101:2631–8.

    Article  PubMed  CAS  Google Scholar 

  16. Neuberger HR, Schotten U, Verheule S, et al. Development of a substrate of atrial fibrillation during chronic atrioventricular block in the goat. Circulation. 2005;111:30–7.

    Article  PubMed  Google Scholar 

  17. Kistler PM, Sanders P, Dodic M, et al. Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation. Eur Heart J. 2006;27:3045–56.

    Article  PubMed  Google Scholar 

  18. Sanders P, Morton JB, Davidson NC, et al. Electrical remodeling of the atria in congestive heart failure: electrophysiological and electroanatomic mapping in humans. Circulation. 2003;108:1461–8.

    Article  PubMed  Google Scholar 

  19. Kistler PM, Sanders P, Fynn SP, et al. Electrophysiologic and electroanatomic changes in the human atrium associated with age. J Am Coll Cardiol. 2004;44:109–16.

    Article  PubMed  Google Scholar 

  20. Anyukhovsky EP, Sosunov EA, Plotnikov A, et al. Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis. Cardiovasc Res. 2002;54:462–9.

    Article  PubMed  CAS  Google Scholar 

  21. Rensma PL, Allessie MA, Lammers WJEP, Bonke FIM, Schalij MJ. Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs. Circ Res. 1988;62:395–410.

    Article  PubMed  CAS  Google Scholar 

  22. Ishiguro YS, Honjo H, Opthof T, et al. Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium. Heart Rhythm. 2009;6:684–92.

    Article  PubMed  Google Scholar 

  23. Kawase A, Ikeda T, Nakazawa K, et al. Widening of the excitable gap and enlargement of the core of reentry during atrial fibrillation with a pure sodium channel blocker in canine atria. Circulation. 2003;107:905–10.

    Article  PubMed  Google Scholar 

  24. Dhein S, Hagen A, Jozwiak J, et al. Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:221–34.

    Article  PubMed  CAS  Google Scholar 

  25. Burstein B, Comtois P, Michael G, et al. Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure. Circ Res. 2009;105:1213–22.

    Article  PubMed  CAS  Google Scholar 

  26. Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention. Europace. 2011;13:308–28.

    Article  PubMed  Google Scholar 

  27. Tan AY, Zhou S, Ogawa M, et al. Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines. Circulation. 2008;118:916–25.

    Article  PubMed  Google Scholar 

  28. Dobrev D, Voigt N, Wehrens XH. The ryanodine receptor channel as a molecular motif in atrial fibrillation: pathophysiological and therapeutic implications. Cardiovasc Res. 2011;89:734–43.

    Article  PubMed  CAS  Google Scholar 

  29. Chou CC, Chen PS. New concepts in atrial fibrillation: neural mechanisms and calcium dynamics. Cardiol Clin. 2009;27:35–43.

    Article  PubMed  Google Scholar 

  30. Burashnikov A, Antzelevitch C. Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early after depolarization-induced triggered activity. Circulation. 2003;107:2355–60.

    Article  PubMed  Google Scholar 

  31. Burashnikov A, Antzelevitch C. Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation. Pacing Clin Electrophysiol. 2006;29:290–5.

    Article  PubMed  Google Scholar 

  32. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation. 2004;109:327–34.

    Article  PubMed  Google Scholar 

  33. Antzelevitch C, Shimizu W, Yan GX, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol. 1999;10:1124–52.

    Article  PubMed  CAS  Google Scholar 

  34. Antzelevitch C, et al. Mechanisms of cardiac arrhythmias and conduction disturbances. In: Fuster V, O’Rourke RA, Walsh RA, editors. Hurst’s the heart. 12th ed. New York: McGraw-Hill; 2008. p. 913–45.

    Google Scholar 

  35. Antzelevitch C, Yan GX. J-wave syndromes. From cell to bedside. J Electrocardiol. 2011;44:656–61.

    Article  PubMed  Google Scholar 

  36. Di Diego JM, Antzelevitch C. Ischemic ventricular arrhythmias experimental models and their clinical relevance. Heart Rhythm. 2011;8:1963–8.

    Article  PubMed  Google Scholar 

  37. Antzelevitch C, Burashnikov A. Overview of basic mechanisms of cardiac arrhythmia. Card Electrophysiol Clin. 2011;3:23–45.

    Article  PubMed  Google Scholar 

  38. Derakhchan K, Villemaire C, Talajic M, Nattel S. The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF. Cardiovasc Res. 2001;50:75–84.

    Article  PubMed  CAS  Google Scholar 

  39. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation. 2007;116:1449–57.

    Article  PubMed  CAS  Google Scholar 

  40. Burashnikov A, Sicouri S, Di Diego JM, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of dronedarone and ranolazine to suppress atrial fibrillation. J Am Coll Cardiol. 2010;56:1216–24.

    Article  PubMed  CAS  Google Scholar 

  41. Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984;24:129–47.

    Article  PubMed  CAS  Google Scholar 

  42. Burashnikov A, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block strategy to suppress atrial fibrillation. Ranolazine versus propafenone. J Pharmacol Exp Ther. 2012;340:161–8.

    Article  PubMed  CAS  Google Scholar 

  43. Burashnikov A, Di Diego JM, Sicouri S, et al. Atrial-selective effects of chronic amiodarone in the management of atrial fibrillation. Heart Rhythm. 2008;5:1735–42.

    Article  PubMed  Google Scholar 

  44. Burashnikov A, Antzelevitch C. Novel pharmacological targets for the rhythm control management of atrial fibrillation. Pharmacol Ther. 2011;132:300–13.

    Article  PubMed  CAS  Google Scholar 

  45. Whalley DW, Wendt DJ, Grant AO. Basic concepts in cellular cardiac electrophysiology: part II: block of ion channels by antiarrhythmic drugs. Pacing Clin Electrophysiol. 1995;18:1686–704.

    Article  PubMed  CAS  Google Scholar 

  46. Carmeliet E, Mubagwa K. Antiarrhythmic drugs and cardiac ion channels: mechanisms of action. Prog Biophys Mol Biol. 1998;70:1–72.

    Article  PubMed  CAS  Google Scholar 

  47. Hondeghem LM, Katzung BG. Mechanism of action of antiarrhythmic drugs. In: Sperelakis N, editor. Physiology and pathophysiology of the heart. 3rd ed. Boston: Kluwer Academic Publishers; 1995. p. 589–603.

    Google Scholar 

  48. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation – executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006;48:854–906.

    Article  PubMed  Google Scholar 

  49. Kumagai K, Nakashima H, Tojo H, et al. Pilsicainide for atrial fibrillation. Drugs. 2006;66:2067–73.

    Article  PubMed  CAS  Google Scholar 

  50. Wu LM, Orikabe M, Hirano Y, Kawano S, Hiraoka M. Effects of Na+ channel blocker, pilsicainide, on HERG current expressed in HEK-293 cells. J Cardiovasc Pharmacol. 2003;42:410–8.

    Article  PubMed  CAS  Google Scholar 

  51. Kneller J, Kalifa J, Zou R, et al. Mechanisms of atrial fibrillation termination by pure sodium channel blockade in an ionically-realistic mathematical model. Circ Res. 2005;96:e35–47.

    Article  PubMed  CAS  Google Scholar 

  52. Comtois P, Sakabe M, Vigmond EJ, et al. Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers. Insights from mathematical models and experimental correlates. Am J Physiol Heart Circ Physiol. 2008;295:H1489–504.

    Article  PubMed  CAS  Google Scholar 

  53. Kirchhof P, Engelen M, Franz MR, et al. Electro_physiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation. Basic Res Cardiol. 2005;100:112–21.

    Article  PubMed  CAS  Google Scholar 

  54. Burashnikov A, Zygmunt AC, Di Diego JM, et al. AZD1305 exerts atrial-predominant electrophysiological actions and is effective in suppressing atrial fibrillation and preventing its re-induction in the dog. J Cardiovasc Pharmacol. 2010;56:80–90.

    Article  PubMed  CAS  Google Scholar 

  55. Wit AL, Rosen MR. After depolarizations and triggered activity: distinction from automaticity as an arrhythmogenic mechanism. In: Fozzard HA et al., editors. The heart and cardiovascular system. New York: Raven; 1992. p. 2113–64.

    Google Scholar 

  56. Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiological basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8:1281–90.

    Article  PubMed  Google Scholar 

  57. Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol. 2011;57:e101–98.

    Article  PubMed  CAS  Google Scholar 

  58. Burstein B, Nattel S. Atrial structural remodeling as an antiarrhythmic target. J Cardiovasc Pharmacol. 2008;52:4–10.

    Article  PubMed  CAS  Google Scholar 

  59. Eijsbouts S, Ausma J, Blaauw Y, et al. Serial cardioversion by class IC drugs during 4 months of persistent atrial fibrillation in the goat. J Cardiovasc Electrophysiol. 2006;17:648–54.

    Article  PubMed  Google Scholar 

  60. Duytschaever M, Blaauw Y, Allessie M. Consequences of atrial electrical remodeling for the anti-arrhythmic action of class IC and class III drugs. Cardiovasc Res. 2005;67:69–76.

    Article  PubMed  CAS  Google Scholar 

  61. Kumar K, Nearing BD, Carvas M, et al. Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart. J Cardiovasc Electrophysiol. 2009;20:796–802.

    Article  PubMed  Google Scholar 

  62. Goldstein RN, Khrestian C, Carlsson L, Waldo AL. Azd7009: a new antiarrhythmic drug with predominant effects on the atria effectively terminates and prevents reinduction of atrial fibrillation and flutter in the sterile pericarditis model. J Cardiovasc Electrophysiol. 2004;15:1444–50.

    Article  PubMed  Google Scholar 

  63. Szel T, Koncz I, Jost N, et al. Class I/B antiarrhythmic property of ranolazine, a novel antianginal agent, in dog and human cardiac preparations. Eur J Pharmacol. 2011;662:31–9.

    Article  PubMed  CAS  Google Scholar 

  64. Bechard J, Pourrier M. Atrial selective effects of intravenously administrated vernakalant in conscious beagle dog. J Cardiovasc Pharmacol. 2011;58:49–55.

    Article  PubMed  CAS  Google Scholar 

  65. Burashnikov A, Pourrier M, Gibson JK, et al. Rate-dependent effects of vernakalant in the isolated non-remodeled canine left atria are primarily due to block of the sodium channel. Comparison with ranolazine and dl-sotaol. Circ Arrhythm Electrophysiol. 2012;5:400–8.

    Google Scholar 

  66. Bogdan R, Goegelein H, Ruetten H. Effect of dronedarone on Na(+), Ca (2+) and HCN channels. Naunyn Schmiedebergs Arch Pharmacol. 2011;383:347–56.

    Article  PubMed  CAS  Google Scholar 

  67. Burashnikov A, Antzelevitch C. Atrial-selective sodium channel block for the treatment of atrial fibrillation. Expert Opin Emerg Drugs. 2009;14:233–49.

    Article  PubMed  CAS  Google Scholar 

  68. Burashnikov A, Antzelevitch C. Atrial-selective sodium channel blockers: do they exist? J Cardiovasc Pharmacol. 2008;52:121–8.

    Article  PubMed  CAS  Google Scholar 

  69. Burashnikov A, Antzelevitch C. New development in atrial antiarrhythmic drug therapy. Nat Rev Cardiol. 2010;7:139–48.

    Article  PubMed  CAS  Google Scholar 

  70. Burashnikov A, Antzelevitch C. How do atrial-selective drugs differ from antiarrhythmic drugs currently used in the treatment of atrial fibrillation? J Atr Fibrillation. 2008;1:98–107.

    PubMed  Google Scholar 

  71. Antzelevitch C, Burashnikov A. Atrial-selective sodium channel block as a novel strategy for the management of atrial fibrillation. J Electrocardiol. 2009;42:543–8.

    Article  PubMed  Google Scholar 

  72. Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace. 2011;13:161–73.

    Article  PubMed  Google Scholar 

  73. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116:1647–52.

    Article  PubMed  CAS  Google Scholar 

  74. Murdock DK, Overton N, Kersten M, Kaliebe J, Devecchi F. The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation. Ind Pacing Electrophysiol J. 2008;8:175–81.

    Google Scholar 

  75. Murdock DK, Kersten M, Kaliebe J, Larrian G. The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a review of experience with implications for possible “pill in the pocket” approach to atrial fibrillation. Ind Pacing Electrophysiol J. 2009;9:260–7.

    Google Scholar 

  76. Murdock DK, Reiffel JA, Kaliebe JW, Larrian G. The conversion of paroxysmal of initial onset of atrial fibrillation with oral ranolazine: implications for “pill in the pocket” approach in structural heart disease. J Am Coll Cardiol. 2010;55:A6.E58.

    Article  Google Scholar 

  77. Crijns HJ, Van Gelder I, Walfridsson H, et al. Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009. Heart Rhythm. 2006;3:1321–31.

    Article  PubMed  Google Scholar 

  78. Geller JC, Egstrup K, Kulakowski P, et al. Rapid conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009. J Clin Pharmacol. 2009;49:312–22.

    Article  PubMed  CAS  Google Scholar 

  79. Ronaszeki A, Alings M, Egstrup K, et al. Pharmacological cardioversion of atrial fibrillation – a double-blind, randomized, placebo-controlled, multicentre, dose-escalation study of AZD1305 given intravenously. Europace. 2011;13:1148–56.

    Article  PubMed  Google Scholar 

  80. Bauer A, Koch M, Kraft P, et al. The new selective IKs-blocking agent HMR 1556 restores sinus rhythm and prevents heart failure in pigs with persistent atrial fibrillation. Basic Res Cardiol. 2005;100:270–8.

    Article  PubMed  CAS  Google Scholar 

  81. Nakashima H, Gerlach U, Schmidt D, Nattel S. In vivo electrophysiological effects of a selective slow delayed-rectifier potassium channel blocker in anesthetized dogs: potential insights into class III actions. Cardiovasc Res. 2004;61:705–14.

    Article  PubMed  CAS  Google Scholar 

  82. Nattel S, Carlsson L. Innovative approaches to anti-arrhythmic drug therapy. Nat Rev Drug Discov. 2006;5:1034–49.

    Article  PubMed  CAS  Google Scholar 

  83. Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation. 2002;105:2753–9.

    Article  PubMed  Google Scholar 

  84. Cha TJ, Ehrlich JR, Chartier D, et al. Kir3-based inward rectifier potassium current: potential role in atrial tachycardia remodeling effects on atrial repolarization and arrhythmias. Circulation. 2006;113:1730–7.

    Article  PubMed  CAS  Google Scholar 

  85. Hashimoto N, Yamashita T, Tsuruzoe N. Tertiapin, a selective IK, ACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation. Pharmacol Res. 2006;54:136–41.

    Article  PubMed  CAS  Google Scholar 

  86. Dobrev D, Friedrich A, Voigt N, et al. The G protein-gated potassium current IK, ACh is constitutively active in patients with chronic atrial fibrillation. Circulation. 2005;112:3697–706.

    Article  PubMed  CAS  Google Scholar 

  87. Voigt N, Friedrich A, Bock M, et al. Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK, ACh channels in patients with chronic atrial fibrillation. Cardiovasc Res. 2007;74:426–37.

    Article  PubMed  CAS  Google Scholar 

  88. Ehrlich JR, Cha TJ, Zhang L, et al. Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium. J Physiol. 2004;557:583–97.

    Article  PubMed  CAS  Google Scholar 

  89. Ravens U. Potassium channels in atrial fibrillation: targets for atrial and pathology-specific therapy? Heart Rhythm. 2008;5:758–9.

    Article  PubMed  Google Scholar 

  90. Ford JW, Milnes JT. New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): rationale, pharmacology and evidence for potential therapeutic value. J Cardiovasc Pharmacol. 2008;52:105–20.

    Article  PubMed  CAS  Google Scholar 

  91. Burashnikov A, Antzelevitch C. Can inhibition of IKur promote atrial fibrillation? Heart Rhythm. 2008;5:1304–9.

    Article  PubMed  Google Scholar 

  92. Ehrlich JR, Nattel S. Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope? Curr Opin Cardiol. 2009;24:50–5.

    Article  PubMed  Google Scholar 

  93. Ravens U, Wettwer E. Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications. Cardiovasc Res. 2011;89:843–51.

    Article  CAS  Google Scholar 

  94. Pandit SV, Zlochiver S, Filgueiras-Rama D, et al. Targeting atrio-ventricular differences in ion channel properties for terminating acute atrial fibrillation in pigs. Cardiovasc Res. 2011;89:843–51.

    Article  PubMed  CAS  Google Scholar 

  95. Feng J, Xu D, Wang Z, Nattel S. Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences. Am J Physiol. 1998;275:H1717–25.

    PubMed  CAS  Google Scholar 

  96. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM. Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res. 1997;80:772–81.

    Article  PubMed  Google Scholar 

  97. Christ T, Wettwer E, Voigt N, et al. Pathology-specific effects of the IKur/Ito/IK, ACh blocker AVE0118 on ion channels in human chronic atrial fibrillation. Br J Pharmacol. 2008;154:1619–30.

    Article  PubMed  CAS  Google Scholar 

  98. Colatsky TJ, Follmer CH, Starmer CF. Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Circulation. 1990;82:2235–42.

    Article  PubMed  CAS  Google Scholar 

  99. Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation. 1990;81:686–90.

    Article  PubMed  CAS  Google Scholar 

  100. Workman AJ, Smith GL, Rankin AC. Mechanisms of termination and prevention of atrial fibrillation by drug therapy. Pharmacol Ther. 2011;131:221–41.

    Article  PubMed  CAS  Google Scholar 

  101. Tse HF, Lau CP. Electrophysiologic actions of dl-sotalol in patients with persistent atrial fibrillation. J Am Coll Cardiol. 2002;40:2150–5.

    Article  PubMed  CAS  Google Scholar 

  102. Spinelli W, Parsons RW, Colatsky TJ. Effects of WAY-123,398, a new class III antiarrhythmic agent, on cardiac refractoriness and ventricular fibrillation threshold in anesthetized dogs: a comparison with UK-68798, E-4031, and dl-sotalol. J Cardiovasc Pharmacol. 1992;20:913–22.

    Article  PubMed  CAS  Google Scholar 

  103. Ehrlich JR, Biliczki P, Hohnloser SH, Nattel S. Atrial-selective approaches for the treatment of atrial fibrillation. J Am Coll Cardiol. 2008;51:787–92.

    Article  PubMed  CAS  Google Scholar 

  104. Burashnikov A, Petroski A, Hu D, Barajas-Martinez H, Antzelevitch C. Atrial-selective inhibition of sodium channel current by Wenxin Keli is effective in suppressing atrial fibrillation. Heart Rhythm. 2012;9:125–31.

    Article  PubMed  Google Scholar 

  105. Blaauw Y, Schotten U, van Hunnik A, Neuberger HR, Allessie MA. Cardioversion of persistent atrial fibrillation by a combination of atrial specific and non-specific class III drugs in the goat. Cardiovasc Res. 2007;75:89–98.

    Article  PubMed  CAS  Google Scholar 

  106. Verheule S, Tuyls E, van Hunnik A, et al. Fibrillatory conduction in the atrial free walls of goats in persistent and permanent atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:590–9.

    Article  PubMed  Google Scholar 

  107. Sicouri S, Burashnikov A, Belardinelli L, Antzelevitch C. Synergistic electrophysiologic and antiarrhythmic effects of the combination of ranolazine and chronic amiodarone in canine atria. Circ Arrhythm Electrophysiol. 2010;3:88–95.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement.

Supported by grants from the National Institutes of Health HL 47678 (CA), NYSTEM # C026424 (CA), the American Heart Association, New York State Affiliate (AB), and the Masons of New York State and Florida.

Author information

Authors and Affiliations

  1. Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA

    Alexander Burashnikov PhD

  2. Gordon K. Moe Scholar, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA

    Charles Antzelevitch PhD, FACC, FAHA, FHRS

Authors
  1. Alexander Burashnikov PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles Antzelevitch PhD, FACC, FAHA, FHRS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles Antzelevitch PhD, FACC, FAHA, FHRS .

Editor information

Editors and Affiliations

  1. , Department of Internal Medicine, UMDNJ-RWJ Medical School, Robert Wood Johnson Pl. 1, New Brunswick, 08903-0019, New Jersey, USA

    Ihor Gussak

  2. , Gordon K. Moe Scholar, Masonic Medical Research Laboratory, Bleecker Street, Utica, 13501-1787, New York, USA

    Charles Antzelevitch

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Burashnikov, A., Antzelevitch, C. (2013). Mechanisms of Action of Antiarrhythmic Drugs in Atrial Fibrillation. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4881-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4881-4_8

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4880-7

  • Online ISBN: 978-1-4471-4881-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation