Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 297, Issue 5, 2009, Pages

  Dhalla, Arvinder K ^a   Wang, Wei Qun ^a   Dow, Joan ^b   Shryock, John C ^a   Belardinelli, Luiz ^a   Bhandari, Anil ^b   Kloner, Robert A ^b,c  

^a CV THERAPEUTICS INC   (United States)

^b GOOD SAMARITAN HOSPITAL   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Arrhythmias; Myocardial ischemia reperfusion; Ranolazine; Ventricular fibrillation; Ventricular tachycardia

Indexed keywords

RANOLAZINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BOLUS INJECTION; CONTROLLED STUDY; DISEASE DURATION; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG MEGADOSE; FEMALE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART MUSCLE REPERFUSION; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE TACHYCARDIA; IN VIVO STUDY; LEFT CORONARY ARTERY; LOW DRUG DOSE; MALE; MORTALITY; NONHUMAN; PRIORITY JOURNAL; RAT; SINGLE DRUG DOSE;

ACETANILIDES; ANGINA PECTORIS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; BLOOD PRESSURE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; INFUSIONS, INTRAVENOUS; INJECTIONS, INTRAVENOUS; MALE; MYOCARDIAL ISCHEMIA; MYOCARDIAL REPERFUSION INJURY; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; TACHYCARDIA, VENTRICULAR; TIME FACTORS; VENTRICULAR FIBRILLATION;

EID: 70449090162     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00173.2009     Document Type: Article

References (28)

1. Antzelevitch C, Belardinelli L. The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis. J Cardiovasc Electrophysiol 17, Suppl 1: S79-S85 2006.
2. Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 113: 2462-2472, 2006.
3. Curtis MJ, Macleod BA, Walker MJ. Models for the study of arrhythmias in myocardial ischaemia and infarction: the use of the rat. J Mol Cell Cardiol 4: 399-419, 1987. (Pubitemid 17099003)
4. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 324: 781-788, 1991.
5. Eng S, Maddaford TG, Kardami E, Pierce GN. Protection against myocardial ischemic/reperfusion injury by inhibitors of two separate pathways of Na+ entry. J Mol Cell Cardiol 30: 829-835, 1998. (Pubitemid 28190727)
6. Gralinski MR, Chi L, Park JL, Friedrichs GS, Tanhehco EJ, McCormack JG, Lucchesi BR. Protective effects of ranolazine on ventricular fibrillation induced by activation of the ATP-dependent potassium channel in the rabbit heart. J Cardiovasc Pharmacol Ther 1: 141-148, 1996.
7. Hagar JM, Hale SL, Kloner RA. Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat. Circ Res 68: 61-68, 1991.
8. Hale SL, Leeka JA, Kloner RA. Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium current. J Pharmacol Exp Ther 318: 418-423, 2006.
9. Hale SL, Kloner RA. Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther 11: 249-255, 2006.
10. Hale SL, Kloner RA. The antianginal agent, ranolazine, reduces myocardial infarct size but does not alter anatomic no-reflow or regional myocardial blood flow in ischemia/reperfusion in the rabbit. J Cardiovasc Pharmacol Ther 13: 226-232, 2008.
11. Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Moll Cell Cardiol 44: 954-967, 2008.
12. Kloner RA, Dow J, Bhandari A. Postconditioning markedly attenuates ventricular arrhythmias after ischemia-reperfusion. J Cardiovasc Pharmacol Ther 11: 55-63, 2006.
13. Ma JH, Luo AT, Zhang PH. Effect of hydrogen peroxide on persistent sodium current in guinea pig ventricular myocytes. Acta Pharmacol Sin 26: 828-834, 2005.
14. Morrow DA, Scirica BM, Karwatowksa-Prokopezuk E, Murphy SA, Buday A, Varshavsky S. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-Elevation in Acute Coronary Syndromes. The MERLIN-TIMI 36 randomized trial. J Am Med Assoc 297: 1775-1783, 2007. (Pubitemid 46658646)
15. Noble D, Noble PJ. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart 92, Suppl 4: iv1-iv5, 2006. (Pubitemid 43974035)
16. Pepine CJ, Wolff AA on behalf of the Ranolazine Study Group. A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Am J Cardiol 84: 46-50, 1999.
17. Reuter H, Seitz N. The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol 195: 45-70, 1968.
18. Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 95: 311-316, 2005. (Pubitemid 40164531)
19. 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 142: 1300-1308, 2004. (Pubitemid 39185852)
20. Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM, Molhoek P, Verheugt FW, Gersh BJ, McCabe CH, Braunwald E. 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-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 116: 1647-1652, 2007. (Pubitemid 47537839)
21. Slezak J, Tribulova N, Pristacova J, Uhrik B, Thomas T, Khaper N, Kaul N, Singal PK. Hydrogen peroxide changes in ischemic and reperfused heart. Am J Pathol 147: 772-781, 1995.
22. Song Y, Shryock JC, Belardinelli L. An increase of late sodium current induces delayed after depolarizations and sustained triggered activity in atrial myocytes. Am J Physiol Heart Circ Physiol 294: H2031-H2039, 2008.
23. 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 318: 214-222, 2006. (Pubitemid 43920758)
24. Tani M, Neely JR. Role of intracellular Na+ in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat heart. Possible involvement of H+-Na+ and Na+-Ca2+ exchange. Circ Res 65: 1045-1056, 1989.
25. Wagner S, Seidler T, Picht E, Maier LS, Kazanski V, Teucher N, Schillinger W, Pieske B, Isenberg G, Hasenfuss G, Kögler H. Na(+)- Ca(2+) exchanger overexpression predisposes to reactive oxygen speciesinduced injury. Cardiovasc Res 60: 404-412, 2003. (Pubitemid 37412374)
26. 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 310: 599-605, 2004. (Pubitemid 38992327)
27. Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac "late sodium current." Pharmacol Ther 119: 326-339, 2008.
28. Zhao G, Messina E, Xu X, Ochoa M, Serpillon S, Shryock J, Belardinelli L, Hintze TH. Ranolazine, a novel anti-anginal agent, does not alter isosorbide dinitrate- or sildenafil-induced changes in blood pressure in conscious dogs. Eur J Pharmacol 541: 171-176, 2006. (Pubitemid 43903483)