2012


To access this material please log in or register

Register Authorize
2012/№6

New pharmacological strategies of atrial fibrillation treatment: accent on atrial selectivity (part II)

Tatarskiy B. A., Biserova I. N.
Federal State Budgetary Institution, “North-West Federal Medical Research Center” of the RF Ministry of Health Care, Akkuratova 2, St.-Petersburg 197341

Keywords: treatment, atrial selectivity, atrial fibrillation

DOI: 10.18087 / rhj.2012.6.1735

The review covers experimental and clinical studies atrium-specific and predominant drugs for treatment of atrial fibrillation (AF). It was shown that the main strategy of arrhythmia suppression and sinus rhythm maintenance remains ion channel inhibition. We assume that drugs blocking several ion channels are more effective for rhythm control than selective blockers. The provided results of the studies carried out indicate that simultaneous blockade fast sodium, potassium and slow sodium channels can be accompanied by selective atrial effect with very low risk of induction ventricular tachycardia.
  1. 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 (6):816–861.
  2. Viskin S, Barron HV, Heller K et al. The treatment of atrial fibrillation: pharmacologic and nonpharmacologic strategies. Curr Probl Cardiol. 1997;22 (2):37–108.
  3. Wang Z, Fermini B, Nattel S. SustaineNaunyn Schmiedebergs Arch Pharmacol. 2004 Sep;370 (3):183–92.d depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ Res. 1993;73 (6):1061–1076.
  4. Feng J, Wible B, Li G et al. S. Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res. 1997 Apr;80 (4):572–579.
  5. Peukert S, Brendel J, Pirard B et al. Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel. Bioorg Med Chem Lett. 2004;14 (11):2823–2827.
  6. Matsuda T, Masumiya H, Tanaka N et al. Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K+ channel Kv1.5 current. Life Sci. 2001;68 (17):2017–2024.
  7. Gögelein H, Brendel J, Steinmeyer K et al. Effects of the atrial antiarrhythmic drug AVE0118 on cardiac ion channels. Naunyn Schmiedebergs Arch Pharmacol. 2004;370 (3):183–192.
  8. Wirth KJ, Paehler T, Rosenstein B et al. Atrial effects of the no­vel K (+) – channel-blocker AVE0118 in anesthetized pigs. Cardiovasc Res. 2003;60 (2):298–306.
  9. Blaauw Y, Gogelein H, Tieleman R et al. «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 (13):1717–1724.
  10. 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 (16):2299–2306.
  11. Courtemanche M, Ramirez RJ, Nattel S. Ionic targets for drug the­rapy and atrial fibrillationinduced electrical remodeling: insights from a mathematical model. Cardiovasc Res. 1999;42 (2):477–489.
  12. %%Rivard L, Shiroshita-Takeshita A, Maltais C et al. Electro­physiological and atrial antiarrhythmic effects of a novel IKur / Kv1.5 blocker in dogs. Heart Rhythm. 2005;2 (Suppl 1):S180.
  13. %%Shiroshita-Takeshita A, Maltais C, Nattel S. et al. Electro­physiological and atrial antiarrhythmic effects of a novel IKur / Kv1.5 blocker in dogs with atrial tachycardia remodeling. Heart Rhythm. 2006;3 (Suppl 1):S183.
  14. Информация с сайта en.sanofi.com. Доступно на: http://en.sanofi-­aventis.com / rd / portfolio / p_rd_portfolio_cardio.asp.
  15. Wirth KJ, Brendel J, Steinmeyer K et al. In vitro and in vivo effects of the atrial selective antiarrhythmic drug. J Cardiovasc Pharmacol. 2007;49 (4):197–206.
  16. Информация с сайта xention.com. Доступно на: http:/­/www.xention.com / 
  17. Regan CP, Stump GL, Wallace AA et al. In vivo cardiac electrophy­siologic and antiarrhythmic effects of an isoquinoline IKur blocker, ISQ-1, in rat, dog, and nonhuman primate. J Cardiovasc Pharmacol. 2007;49 (4):236–245.
  18. Lloyd J, Atwal KS, Finlay HJ et al. Benzopyran sulfonamides as KV1.5 potassium channel blockers. Bioorg Med Chem Lett. 2007;17 (12):3271–3275.
  19. 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 (14):1730–1737.
  20. Ehrlich JR, Cha TJ, Zhang L et al. Characterization of a hyperpolarization activated time-dependent potassiumm current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium. J Physiol. 2004;557 (Pt 2):583–597.
  21. Dobrev D, Friedrich A, Voigt N et al. The G protein-gated potassium current I (K,ACh) is constitutively active in patients with chronic atrial fibrillation. Circulation. 2005;112 (24):3697–3706.
  22. Fedida, D. Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent. Expert Opin Investig Drugs. 2007;16 (4):519–532.
  23. Roy D, Rowe BH, Stiell IG et al, for the CRAFT Investigators. A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. J Am Coll Cardiol. 2004 Dec 21;44 (12):2355–2361.
  24. Pratt C, Navratil J, Nagy A. Oral vernakalant (RSD1235‑SR) prevents recurrence of atrial fibrillation following cardioversion. Heart Rhythm. 2007;4 (Suppl 1):S176.
  25. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E et al. MERLIN-TIMI 36 Investigators. Evaluation of a novel anti-ische­mic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN) – TIMI 36 trial. JAMA. 2007;297 (16):1775–1783.
  26. Fedida D, Orth PM, Chen JY et al. The mechanism of atrial antiarrhythmic action of RSD1235. J Cardiovasc Electrophysiol. 2005;16 (11):1227–1238.
  27. Orth PM, Hesketh JC, Mak CK et al. RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents. Cardiovasc Res. 2006;70 (3):486–496.
  28. Sicouri S, Glass A, Antzelevitch C. Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations.Heart Rhythm. 2008;5 (7):1019–1026.
  29. Dorian P, Pinter A, Mangat I et al. The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans. J Cardiovasc Pharmacol. 2007;50 (1):35–40.
  30. %%Antzelevitch C, Burashnikov A, Sicouri S. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8 (8):1281–1290.
  31. Sossalla S, Kallmeyer B, Wagner S, et al. Altered Naю currents in atrial fibrillation: effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol. 2010;55 (21):2330–2342.
  32. Burashnikov A, Sicouri S, Antzelevitch C. et al. Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation. J Am Coll Cardiol. 2010;56 (15):1216–1224.
  33. Burashnikov A, Di Diego JM, Zygmunt AC et al. 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 (13):1449–1457.
  34. Murdock D, Overton N, Kersten M. et al. The effect of ranolazine on maintaining sinus rhythm in patient with resistant atrial fibrillation. Indian Pacing Electrophysiol J.2008;8 (3):175–181.
  35. Murdock DK, Kersten M, Kaliebe J, Larrain 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. Indian Pacing Electrophysiol J. 2009;9 (5):260–267.
  36. Miles R, Passman R, Murdock D. Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting. Am J Cardiol. 2011;108 (5):673–676.
  37. Schotten U, Verheule S, Kerfant BG, Greiser M. Enhanced late Na currents in atrial fibrillation: new drug target or just an epiphenomenon? J Am Coll Cardiol. 2010;55 (21):2343–2345.
  38. Wang P, Fraser H, Lloyd S et al. A comparison between ranolazine and CVT-4325, a novel inhibitor of fatty acid oxidation, on cardiac metabolism and left ventricular function in rat isolated perfused heart during ischemia and reperfusion. J Pharmacol Exp Ther. 2007;321 (1): 213–220.
  39. Lemoine M, Duverger J, Naud P et al. Arrhythmogenic left atrial cellular electrophysiology in a murine genetic long QT syndrome model. Cardiovasc Res. 2011;92 (1):67–74.
Tatarskiy B. A., Biserova I. N. New pharmacological strategies of atrial fibrillation treatment: accent on atrial selectivity (part II). Russian Heart Journal. 2012;11(6):369-375.

To access this material please log in or register

Register Authorize
Ru En