Late sodium current inhibition in acquired and inherited ventricular (dys)function and arrhythmias

Cardiovascular Drugs and Therapy

Volumn 27, Issue 1, 2013, Pages 91-101

  Remme, Carol Ann ^a,b   Wilde, Arthur A M ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

Arrhythmias; Heart failure; Late sodium current; Long QT syndrome; Myocardial ischemia; Pharmacology

Indexed keywords

AMIODARONE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; FLECAINIDE; GS 458967; MEXILETINE; PLACEBO; QUINIDINE; RANOLAZINE; SODIUM CALCIUM EXCHANGE PROTEIN; SODIUM CHANNEL; SODIUM CHANNEL BLOCKING AGENT; SODIUM CHANNEL NAV1.5; UNCLASSIFIED DRUG;

ANGINA PECTORIS; ANTIARRHYTHMIC ACTIVITY; DEFIBRILLATION; DIASTOLIC DYSFUNCTION; DRUG EFFICACY; DRUG SELECTIVITY; DRUG TARGETING; EXERCISE TOLERANCE; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART DEPOLARIZATION; HEART ELECTROPHYSIOLOGY; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEART VENTRICLE ARRHYTHMIA; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE TACHYCARDIA; HUMAN; LIVER TOXICITY; LONG QT SYNDROME; LUNG FIBROSIS; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SODIUM CURRENT;

ANTI-ARRHYTHMIA AGENTS; ARRHYTHMIAS, CARDIAC; GENETIC DISEASES, INBORN; HUMANS; TREATMENT OUTCOME; VENTRICULAR DYSFUNCTION; VOLTAGE-GATED SODIUM CHANNEL BLOCKERS; VOLTAGE-GATED SODIUM CHANNELS;

EID: 84873059580     PISSN: 09203206     EISSN: 15737241     Source Type: Journal    
DOI: 10.1007/s10557-012-6433-x     Document Type: Review

References (88)

1. Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac "late sodium current". Pharmacol Ther. 2008;119(3):326-39.
2. Saint DA. The cardiac persistent sodium current: an appealing therapeutic target? Br J Pharmacol. 2008;153(6):1133-42.
3. Remme CA, Bezzina CR. Sodium channel (dys)function and cardiac arrhythmias. Cardiovasc Ther. 2010;28:287-94.
4. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324(12):781-8.
5. Lu HR, Rohrbacher J, Vlaminckx E, Van Ammel K, Yan GX, Gallacher DJ. Predicting drug-induced slowing of conduction and pro-arrhythmia: identifying the 'bad' sodium current blockers. Br J Pharmacol. 2010;160(1):60-76.
6. Wang DW, Kiyosue T, Sato T, Arita M. Comparison of the effects of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K + current of guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1996;28(5):893-903.
7. Paul AA, Witchel HJ, Hancox JC. Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine. Br J Pharmacol. 2002;136(5):717-29.
8. Kim HS, Pak HN, Park JS, Kim SS. Flecainide-Associated Bradycardia-Dependent Torsade de Pointes: Another Potential Mechanism of Proarrhythmia. Pacing Clin Electrophysiol. 2010:1-3. doi: 10.1111/j.1540-8159. 2010.02935.x.
9. Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome. Circulation. 1997;96(6):2038-47.
10. Shimizu W, Aiba T, Antzelevitch C. Specific therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome. Curr Pharmaceut Design. 2005;11:1561-72.
11. Szél 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(1-3):31-9.
12. Ju YK, Saint DA, Gage PW. Effects of lignocaine and quinidine on the persistent sodium current in rat ventricular myocytes. Br J Pharmacol. 1992;107(2):311-6.
13. Iost N, Virág L, Varró A, Papp JG. Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes. J Cardiovasc Pharmacol Ther. 2003;8(1):31-41.
14. Kodama I, Kamiya K, Toyama J. Cellular electropharmacology of amiodarone. Cardiovasc Res. 1997;35(1):13-29.
15. 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(5):923-32.
16. Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Hear Rhythm. 2011;8(8):1281-90.
17. Undrovinas AI, Belardinelli L, Undrovinas NA, Sabbah HN. Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current. J Cardiovasc Electrophysiol. 2006;17 Suppl 1:S169-77.
18. Fredj S, Sampson KJ, Liu H, Kass RS. Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol. 2006;148(1):16-24.
19. 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;116:1449-57.
20. Zygmunt AC, Nesterenko VV, Rajamani S, et al. Mechanisms of atrial-selective block of sodium channel by ranolazine I. Experimental analysis of the use-dependent block. Am J Physiol Heart Circ Physiol. 2011;301:H1606-14.
21. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation. 2004;110(8):904-10.
22. Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92 Suppl 4:iv6-iv14.
23. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375-82.
24. Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007;49(10):1027-34.
25. Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008;19(12):1289-93.
26. Bunch TJ, Mahapatra S, Murdock D, et al. Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks. Pacing Clin Electrophysiol. 2011;34(12):1600-6.
27. Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, Nattel S. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol. 2004;142(8):1300-8.
28. Rajamani S, Shryock JC, Belardinelli L. Rapid kinetic interactions of ranolazine with HERG K + current. J Cardiovasc Pharmacol. 2008;51(6):581-9.
29. Smith-Maxwell CJ, Xie C, Chan K, et al. Discovery of GS-458967: a novel and highly-selective inhibitor of cardiac sodium channel late current. Hear Rhythm. 2012;9(5,Suppl):S394.
30. Belardinelli L, Liu G, Smith-Maxwell C, et al. A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias. J Pharmacol Exp Ther. 2012 Sep 25. [Epub ahead of print]
31. Sicouri S, Blazek J, Belardinelli L, Antzelevitch C. Antiarrhythmic effects of the highly-selective late sodium channel current blocker GS 458967 in canine purkinje fibers and pulmonary vein sleeve preparations. Hear Rhythm. 2012;9(5, Suppl):S186.
32. Pieske B, Houser SR. [Na+]i handling in the failing human heart. Cardiovasc Res. 2003;57(4):874-86.
33. Noble D, Noble PJ. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart. 2006;92 Suppl 4:iv1-5.
34. Bers DM. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol. 2008;70:23-49.
35. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. ERICA Investigators. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48(3):566-75.
36. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297(16):1775-83.
37. Moreno JD, Clancy CE. Pathophysiology of the cardiac late Na current and its potential as a drug target. J Mol Cell Cardiol. 2012;52(3):608-19.
38. Valdivia CR, Chu WW, Pu J, et al. Increased late sodium current in myocytes from a canine heart failure model and from failing human heart. J Mol Cell Cardiol. 2005;38(3):475-83.
39. Maltsev VA, Undrovinas A. Late sodium current in failing heart: friend or foe? Prog Biophys Mol Biol. 2008;96(1-3):421-51.
40. Maier LS. A novel mechanism for the treatment of angina, arrhythmias, and diastolic dysfunction: inhibition of late I(Na) using ranolazine. J Cardiovasc Pharmacol. 2009;54(4):279-86.
41. Maltsev VA, Reznikov V, Undrovinas NA, Sabbah HN, Undrovinas A. Modulation of late sodium current by Ca2+, calmodulin, and CaMKII in normal and failing dog cardiomyocytes: similarities and differences. Am J Physiol Heart Circ Physiol. 2008;294(4):H1597-608.
42. Xi Y, Wu G, Yang L, et al. Increased late sodium currents are related to transcription of neuronal isoforms in a pressure-overload model. Eur J Heart Fail. 2009;11(8):749-57.
43. Wagner S, Maier LS. Modulation of cardiac Na(+) and Ca(2+) currents by CaM and CaMKII. J Cardiovasc Electrophysiol. 2006;17 Suppl 1:S26-33.
44. Undrovinas NA, Maltsev VA, Belardinelli L, Sabbah HN, Undrovinas A. Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure. J Physiol Sci. 2010;60(4):245-57.
45. Chandler MP, Stanley WC, Morita H, et al. Short-term treatment with ranolazine improves mechanical efficiency in dogs with chronic heart failure. Circ Res. 2002;91(4):278-80.
46. Rastogi S, Sharov VG, Mishra S, et al. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295(5):H2149-55.
47. Lovelock JD, Monasky MM, Jeong EM, et al. Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity. Circ Res. 2012;110(6):841-50.
48. Sossalla S, Wagner S, Rasenack EC, et al. Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts - role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol. 2008;45(1):32-43.
49. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006;41(6):1031-8.
50. Hale SL, Kloner RA. Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006;11(4):249-55.
51. Aldakkak M, Camara AK, Heisner JS, et al. Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts. Pharmacol Res. 2011;64(4):381-92.
52. Sossalla S, Maier LS. Role of ranolazine in angina, heart failure, arrhythmias and diabetes. Pharmacol Ther. 2012;133:311-23.
53. Hayashida W, van Eyll C, Rousseau MF, Pouleur H. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther. 1994;8(5):741-7.
54. Figueredo VM, Pressman GS, Romero-Corral A, Murdock E, Holderbach P, Morris DL. Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina. J Cardiovasc Pharmacol Ther. 2011;16(2):168-72.
55. Jacobshagen C, Belardinelli L, Hasenfuss G, Maier LS. Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study. Clin Cardiol. 2011;34(7):426-32.
56. Spoladore R, Maron MS, D'Amato R, Camici PG, Olivotto I. Pharmacological treatment options for hypertrophic cardiomyopathy: high time for evidence. Eur Heart J. 2012;33(14):1724-33.
57. Song Y, Shryock JC, Wu L, Belardinelli L. Antagonism by ranolazine of the pro-arrhythmic effects of increasing late INa in guinea pig ventricular myocytes. J Cardiovasc Pharmacol. 2004;44(2):192-9.
58. Song Y, Shryock JC, Belardinelli L. An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes. Am J Physiol Heart Circ Physiol. 2008;294(5):H2031-9.
59. Wu L, Shryock JC, Song Y, Li Y, Antzelevitch C, Belardinelli L. Antiarrhythmic effects of ranolazine in a guinea pig in vitro model of long-QT syndrome. J Pharmacol Exp Ther. 2004;310(2):599-605.
60. Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44(6):954-67.
61. Zipes DP, Wellens HJJ. Sudden cardiac death. Circulation. 1998;98:2334-51.
62. Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev. 1989;69:1049.
63. The Cardiac Arrhythmia Suppression Trial. NEJM. 1989;321:406.
64. Song Y, Shryock JC, Wagner S, Maier LS, Belardinelli L. Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther. 2006;318(1):214-22.
65. Zhang XQ, Yamada S, Barry WH. Ranolazine inhibits an oxidative stress-induced increase in myocyte sodium and calcium loading during simulated-demand ischemia. J Cardiovasc Pharmacol. 2008;51(5):443-9.
66. Dhalla AK, Wang WQ, Dow J, et al. Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2009;297(5):H1923-9.
67. Kloner RA, Dow JS, Bhandari A. The antianginal agent ranolazine is a potent antiarrhythmic agent that reduces ventricular arrhythmias: through a mechanism favoring inhibition of late sodium channel. Cardiovasc Ther. 2011;29(4):e36-41.
68. Morita N, Lee JH, Xie Y, et al. Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine. J Am Coll Cardiol. 2011;57(3):366-75.
69. Nieminen T, Nanbu DY, Datti IP, et al. Antifibrillatory effect of ranolazine during severe coronary stenosis in the intact porcine model. Hear Rhythm. 2011;8(4):608-14.
70. 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(15):1647-52.
71. Nanda S, Levin V, Martinez MW, Freudenberger R. Ranolazine-treatment of ventricular tachycardia and symptomatic ventricular premature beats in ischemic cardiomyopathy. Pacing Clin Electrophysiol. 2010;33(12):e119-20.
72. Nattel S, Maguy A, Le Bouter S, Yeh YH. Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev. 2007;87(2):425-56.
73. Janse MJ. Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc Res. 2004;61:208-17.
74. Sossalla S, Maurer U, Schotola H, et al. Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIδ(C) can be reversed by inhibition of late Na(+) current. Basic Res Cardiol. 2011;106(2):263-72.
75. Antoons G, Oros A, Beekman JD, et al. Late na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol. 2010;55(8):801-9.
76. Murdock DK, Kaliebe J, Overton N. Ranolozine-induced suppression of ventricular tachycardia in a patient with nonischemic cardiomyopathy: a case report. Pacing Clin Electrophysiol. 2008;31(6):765-8.
77. Kaliebe JW, Murdock DK. Suppression of non-sustained ventricular tachycardia with ranolazine: a case report. WMJ. 2009;108(7):373-5.
78. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001;103(1):89-95.
79. Zareba W, Sattari MN, Rosero S, et al. Altered atrial, atrioventricular, and ventricular conduction in patients with the long QT syndrome caused by the DeltaKPQ SCN5A sodium channel gene mutation. Am J Cardiol. 2001;88:1311-4.
80. Remme CA, Wilde AA, Bezzina CR. Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends Cardiovasc Med. 2008;18(3):78-87.
81. Lindegger N, Hagen BM, Marks AR, Lederer WJ, Kass RS. Diastolic transient inward current in long QT syndrome type 3 is caused by Ca2+ overload and inhibited by ranolazine. J Mol Cell Cardiol. 2009;47(2):326-34.
82. Remme CA, Verkerk AO, Nuyens D, et al. Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation. 2006;114(24):2584-94.
83. /+ mice. Hear Rhythm. 2010;7(5,Suppl):S160.
84. Wu J, Cheng L, Lammers WJ, et al. Sinus node dysfunction in ATX-II-induced in-vitro murine model of long QT3 syndrome and rescue effect of ranolazine. Prog Biophys Mol Biol. 2008;98(2-3):198-207.
85. Mönnig G, Köbe J, Löher A, et al. Implantable cardioverter-defibrillator therapy in patients with congenital long-QT syndrome: a long-term follow-up. Hear Rhythm. 2005;2(5):497-504.
86. Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;1:19-31.
87. Sicouri S, Timothy KW, Zygmunt AC, et al. Cellular basis for the electrocardiographic and arrhythmic manifestations of timothy syndrome: effects of ranolazine. Hear Rhythm. 2007;4:638-47.
88. Shah DP, Baez-Escudero JL, Weisberg IL, Beshai JF, Burke MC. Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). Pacing Clin Electrophysiol. 2012;35(3):e62-4.