Effects of Ranolazine on Torsades de Pointes Tachycardias in a Healthy Isolated Rabbit Heart Model

Cardiovascular Therapeutics

Volumn 32, Issue 4, 2014, Pages 170-177

  Sossalla, Samuel ^a,b   Wallisch, Nora ^a   Toischer, Karl ^a   Sohns, Christian ^a   Vollmann, Dirk ^a   Seegers, Joachim ^a,c   Lüthje, Lars ^a   Maier, Lars S ^a,c   Zabel, Markus ^a,b  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^c UNIVERSITY HOSPITAL REGENSBURG   (Germany)

Author keywords

Action potential duration; Arrhythmias; Ranolazine; Sotalol; Torsades de Pointes

Indexed keywords

POTASSIUM; POTASSIUM CHANNEL; RANOLAZINE; SOTALOL; ACETANILIDE DERIVATIVE; ANTIARRHYTHMIC AGENT; PIPERAZINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARRHYTHMOGENESIS; ARTICLE; CONTROLLED STUDY; DISPERSION; DRUG EFFECT; ELECTROCARDIOGRAPHY; ENDOCARDIUM; HEART MUSCLE POTENTIAL; HEART REPOLARIZATION; ISOLATED HEART; NONHUMAN; PRIORITY JOURNAL; RABBIT; TACHYCARDIA; TORSADE DES POINTES; VALIDATION PROCESS; ACTION POTENTIAL; ANIMAL; DOSE RESPONSE; DRUG EFFECTS; HEART MUSCLE CONDUCTION SYSTEM; HEART PACING; HEART RATE; IN VITRO STUDY; PATHOPHYSIOLOGY; PERFUSION; TIME; TORSADES DE POINTES;

ACETANILIDES; ACTION POTENTIALS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; CARDIAC PACING, ARTIFICIAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HEART CONDUCTION SYSTEM; HEART RATE; IN VITRO TECHNIQUES; PERFUSION; PIPERAZINES; POTASSIUM; RABBITS; RANOLAZINE; SOTALOL; TIME FACTORS; TORSADES DE POINTES;

EID: 84903955782     PISSN: 17555914     EISSN: 17555922     Source Type: Journal    
DOI: 10.1111/1755-5922.12078     Document Type: Article

References (40)

1. Dorian P, Newman D. Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: An overview. Europace 2000;2:277-285.
2. Wu L, Ma J, Li H, et al. Late sodium current contributes to the reverse rate-dependent effect of IKr inhibition on ventricular repolarization. Circulation 2011;123:1713-1720.
3. Sossalla S, Maier LS. Role of ranolazine in angina, heart failure, arrhythmias, and diabetes. Pharmacol Ther 2012;133:311-322.
4. 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.
5. + current in human ventricle: Implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol 2006;17(Suppl 1):S15-S20.
6. Maltsev VA, Sabbah HN, Higgins RS, Silverman N, Lesch M, Undrovinas AI. Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation 1998;98:2545-2552.
7. + pump function is unchanged. Circulation 2002;105:2543-2548.
8. 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;38:475-483.
9. Ju YK, Saint DA, Gage PW. Hypoxia increases persistent sodium current in rat ventricular myocytes. J Physiol 1996;497:337-347.
10. 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;318:214-222.
11. 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;116:1647-1652.
12. Maltsev VA, Silverman N, Sabbah HN, Undrovinas AI. Chronic heart failure slows late sodium current in human and canine ventricular myocytes: Implications for repolarization variability. Eur J Heart Fail 2007;9:219-227.
13. 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:H2031-H2039.
14. Bers DM. Excitation-contraction coupling and cardiac contractile force, 2nd edn. Dordrecht, Netherlands: Kluwer Academic Publishers, 2001.
15. Lederer WJ, Tsien RW. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol 1976;263:73-100.
16. 2+/calmodulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 2010;107:1150-1161.
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-S177.
18. 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;45:32-43.
19. Na in guinea pig ventricular myocytes. J Cardiovasc Pharmacol 2004;44:192-199.
20. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004;110:904-910.
21. Rajamani S, Shryock JC, Belardinelli L. Rapid kinetic interactions of ranolazine with HERG K+ current. J Cardiovasc Pharmacol 2008;51:581-589.
22. Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006;113:2462-2472.
23. Zabel M, Hohnloser SH, Behrens S, Woosley RL, Franz MR. Differential effects of D-sotalol, quinidine, and amiodarone on dispersion of ventricular repolarization in the isolated rabbit heart. J Cardiovasc Electrophysiol 1997;8:1239-1245.
24. Zabel M, Hohnloser SH, Behrens S, Li YG, Woosley RL, Franz MR. Electrophysiologic features of torsades de pointes: Insights from a new isolated rabbit heart model. J Cardiovasc Electrophysiol 1997;8:1148-1158.
25. Zabel M, Portnoy S, Franz MR. Electrocardiographic indexes of dispersion of ventricular repolarization: An isolated heart validation study. J Am Coll Cardiol 1995;25:746-752.
26. Milberg P, Frommeyer G, Kleideiter A, et al. Antiarrhythmic effects of free polyunsaturated fatty acids in an experimental model of LQT2 and LQT3 due to suppression of early afterdepolarizations and reduction of spatial and temporal dispersion of repolarization. Heart Rhythm 2011;8:1492-1500.
27. Milberg P, Pott C, Fink M, et al. Inhibition of the Na+/Ca2+ exchanger suppresses torsades de pointes in an intact heart model of long QT syndrome-2 and long QT syndrome-3. Heart Rhythm 2008;5:1444-1452.
28. Sossalla S, Sohns C, Seegers J, Luthje L, Vollmann D, Zabel M. Ranolazine maintained sinus rhythm in a patient with refractory symptomatic atrial fibrillation. Cardiovasc Ther 2013;31:303-306.
29. Frommeyer G, Milberg P, Uphaus T, Kaiser D, Kaese S, Breithardt G, Eckardt L. Antiarrhythmic effect of ranolazine in combination with class-III drugs in an experimental whole heart model of atrial fibrillation. Cardiovasc Ther 2013;31:e63-e71.
30. 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;116:1449-1457.
31. Miles RH, Murdock DK. Ranolazine verses amiodarone for prophylaxis against atrial fibrillation following coronary artery bypass surgery. Heart Rhythm 2010;7:258.
32. + currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol 2010;55:2330-2342.
33. Toischer K, Hartmann N, Wagner S, et al. Role of late sodium current as a potential arrhythmogenic mechanism in the progression of pressure-induced heart disease. J Mol Cell Cardiol 2013;61:111-122.
34. Frommeyer G, Kaiser D, Uphaus T, et al. Effect of ranolazine on ventricular repolarization in class III antiarrhythmic drug-treated rabbits. Heart Rhythm 2012;9:2051-2058.
35. Surawicz B. Electrophysiologic substrate of torsade de pointes: Dispersion of repolarization or early afterdepolarizations? J Am Coll Cardiol 1989;14:172-184.
36. Wu L, Rajamani S, Li H, January CT, Shryock JC, Belardinelli L. Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na(+) current in the heart. Am J Physiol Heart Circ Physiol 2009;297:H1048-H1057.
37. Antzelevitch C, Belardinelli L. The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis. J Cardiovasc Electrophysiol 2006;17(Suppl 1):S79-S85.
38. Antzelevitch C, Sicouri S, Litovsky SH, et al. Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ Res 1991;69:1427-1449.
39. Wang WQ, Robertson C, Dhalla AK, Belardinelli L. Antitorsadogenic effects of ({+/-})-N-(2, 6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits. J Pharmacol Exp Ther 2008;325:875-881.
40. + current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol 2010;55:801-809.