Journal of Electrocardiology
Volume 42, Issue 6 , Pages 543-548 , November 2009

Atrial-selective sodium channel block as a novel strategy for the management of atrial fibrillation

Received 11 April 2009

References 

  1. 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
  2. Reiffel JA. Rate vs. rhythm control pharmacotherapy for atrial fibirillation. J Atrial Fibrillation. 2008;1:31
  3. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2007;4:816
  4. Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev. 2005;85:1205
  5. Tamargo J, Caballero R, Gomez R, Valenzuela C, Delpon E. Pharmacology of cardiac potassium channels. Cardiovasc Res. 2004;62:9
  6. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954
  7. Nattel S, Burstein B, Dobrev D. Atrial remodeling and atrial fibrillation: mechanisms and implications. Circ Arrhythm Electrophysiol. 2008;1:62
  8. Nattel S, Carlsson L. Innovative approaches to anti-arrhythmic drug therapy. Nat Rev Drug Discov. 2006;5:1034
  9. 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
  10. Fedida D. Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent. Expert Opin Investig Drugs. 2007;16:519
  11. Carlsson L, Chartier D, Nattel S. Characterization of the in vivo and in vitro electrophysiological effects of the novel antiarrhythmic agent AZD7009 in atrial and ventricular tissue of the dog. J Cardiovasc Pharmacol. 2006;47:123
  12. Blaauw Y, Gogelein H, Tieleman RG, van HA, Schotten U, Allessie MA. “Early” class III drugs for the treatment of atrial fibrillation: efficacy and atrial selectivity of AVE0118 in remodeled atria of the goat. Circulation. 2004;110:1717
  13. 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
  14. 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
  15. 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
  16. Wettwer E, Hala O, Christ T, et al. Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation. Circulation. 2004;110:2299
  17. Burashnikov A, Antzelevitch C. Can inhibition of IKur promote atrial fibrillation?. Heart Rhythm. 2008;5:1304
  18. Burashnikov A, Antzelevitch C. How do atrial-selective drugs differ from antiarrhythmic drugs currently used in the treatment of atrial fibrillation?. J Atrial Fibrillation. 2008;1:98
  19. Ehrlich JR, Nattel S. Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?. Curr Opin Cardiol. 2009;24:50
  20. Burashnikov A, Antzelevitch C. New pharmacological strategies for the treatment of atrial fibrillation. Ann Noninvasive Electrocardiol. 2009;14:290
  21. Olson TM, Alekseev AE, Liu XK, et al. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum Mol Genet. 2006;15:2185
  22. 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
  23. Burashnikov A, Di Diego JM, Sicouri S, Ferreiro M, Carlsson L, Antzelevitch C. Atrial-selective effects of chronic amiodarone in the management of atrial fibrillation. Heart Rhythm. 2008;5:1735
  24. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block as a strategy for suppression of atrial fibrillation. Ann N Y Acad Sci. 2008;1123:105
  25. Burashnikov A, Antzelevitch C. Atrial-selective sodium channel blockers: do they exist?. J Cardiovasc Pharmacol. 2008;52:121
  26. Burashnikov A, Belardinelli L, Antzelevitch C. Ranolazine and propafenone both suppress atrial fibrillation but ranolazine unlike propafenone does it without prominent effects on ventricular myocardium. Heart Rhythm. 2007;4:S163;Abstract
  27. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiologic effects of ranolazine: a novel anti-anginal agent with antiarrhythmic properties. Circulation. 2004;110:904
  28. Kodama I, Kamiya K, Toyama J. Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. Am J Cardiol. 1999;84:20R
  29. Singh BN. Amiodarone as paradigm for developing new drugs for atrial fibrillation. J Cardiovasc Pharmacol. 2008;52:300
  30. Whalley DW, Wendt DJ, Grant AO. Basic concepts in cellular cardiac electrophysiology: part II: block of ion channels by antiarrhythmic drugs. PACE. 1995;18:1686
  31. Carmeliet E, Mubagwa K. Antiarrhythmic drugs and cardiac ion channels: mechanisms of action. Prog Biophys Mol Biol. 1998;70:1
  32. Hondeghem LM, Katzung BG. Mechanism of action of antiarrhythmic drugs. In:  Sperelakis N editors. Physiology and pathophysiology of the heart. 3rd ed.. Boston (MA): Kluwer Academic Publishers; 1995;p. 589
  33. Wang GK, Calderon J, Wang SY. State- and use-dependent block of muscle Nav1.4 and neuronal Nav1.7 noltage-gated Na+ channel isoforms by ranolazine. Mol Pharmacol. 2008;73:940
  34. Shah RR, Hondeghem LM. Refining detection of drug-induced proarrhythmia: QT interval and TRIaD. Heart Rhythm. 2005;2:758
  35. Kodama I, Kamiya K, Toyama J. Cellular electropharmacology of amiodarone. Cardiovasc Res. 1997;35:13
  36. Golod DA, Kumar R, Joyner RW. Determinants of action potential initiation in isolated rabbit atrial and ventricular myocytes. Am J Physiol. 1998;274:H1902
  37. Hiroe K, Hisatome I, Tanaka Y, et al. Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194. Fundam Clin Pharmacol. 1997;11:402
  38. Li GR, Lau CP, Shrier A. Heterogeneity of sodium current in atrial vs epicardial ventricular myocytes of adult guinea pig hearts. J Mol Cell Cardiol. 2002;34:1185
  39. Sakakibara Y, Wasserstrom JA, Furukawa T, et al. Characterization of the sodium current in single human atrial myocytes. Circ Res. 1992;71:535
  40. Sakakibara Y, Furukawa T, Singer DH, et al. Sodium current in isolated human ventricular myocytes. Am J Physiol. 1993;265:H1301
  41. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol. 2003;14:885
  42. Tyrrell L, Renganathan M, Dib-Hajj SD, Waxman SG. Glycosylation alters steady-state inactivation of sodium channel Nav1.9/NaN in dorsal root ganglion neurons and is developmentally regulated. J Neurosci. 2001;21:9629
  43. Investigators CAST. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406
  44. Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006;113:2462
  45. 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
  46. Murdock DK, Overton N, Kersten M, Kaliebe J, Devecchi F. The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation. Indian Pacing Electrophysiol J. 2008;8:175
  47. Antzelevitch C, Belardinelli L, Wu L, et al. Electrophysiologic properties and antiarrhythmic actions of a novel anti-anginal agent. J Cardiovasc Pharmacol Therapeut. 2004;9(Suppl 1):S65
  48. Maltsev VA, Sabbah HN, Undrovinas AI. Late sodium current is a novel target for amiodarone: studies in failing human myocardium. J Mol Cell Cardiol. 2001;33:923
  49. Antzelevitch C. Electrical heterogeneity, cardiac arrhythmias, and the sodium channel. Circ Res. 2000;87:964
  50. Shryock JC, Belardinelli L. Inhibition of late sodium current to reduce electrical and mechanical dysfunction of ischaemic myocardium. Br J Pharmacol. 2008;153:1128
  51. Blaauw Y, Schotten U, van HA, 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
  52. 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
  53. Linz DK, Afkham F, Itter G, Rutten H, Wirth KJ. Effect of atrial electrical remodeling on the efficacy of antiarrhythmic drugs: comparison of amiodarone with IKr- and Ito/IKur-blockade in vivo strial electrical remodeling and antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2007;18:1313
  54. Gaspo R, Bosch RF, Bou-Abboud E, Nattel S. Tachycardia-induced changes in Na+ current in a chronic dog model of atrial fibrillation. Circ Res. 1997;81:1045
  55. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V. Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res. 1999;44:121
  56. Eijsbouts S, Ausma J, Blaauw Y, Schotten U, Duytschaever M, Allessie MA. Serial cardioversion by class IC drugs during 4 months of persistent atrial fibrillation in the goat. J Cardiovasc Electrophysiol. 2006;17:648

 This study was supported by grant HL47678 from NHLBI (CA) and Masons of NYS and Florida.

PII: S0022-0736(09)00275-1

doi: 10.1016/j.jelectrocard.2009.07.007

Journal of Electrocardiology
Volume 42, Issue 6 , Pages 543-548 , November 2009