The role of the Na +/Ca 2+ exchanger, I Na and I CaL in the genesis of dofetilide-induced torsades de pointes in isolated, AV-blocked rabbit hearts

British Journal of Pharmacology

Volumn 156, Issue 6, 2009, Pages 920-932

  Farkas, Attila S ^a,b   Makra, Péter ^a   Csík, Norbert ^c   Orosz, Szabolcs ^d   Shattock, Michael J ^e   Fülöp, Ferenc ^a   Forster, Tamás ^a   Csanády, Miklós ^a   Papp, Julius Gy ^a,b   Varró, András ^a,b   Farkas, András ^a  

^a UNIVERSITY OF SZEGED   (Hungary)

^b INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^c JOHN VON NEUMANN UNIVERSITY   (Hungary)

^d GEDEON RICHTER LTD   (Hungary)

^e Rayne Institute   (United Kingdom)

Author keywords

Isolated heart; Lidocaine; NCX; QT variability; Rabbit; SEA0400; Torsades de pointes; Verapamil

Indexed keywords

2 [4 (2,5 DIFLUOROBENZYLOXY)PHENOXY] 5 ETHOXYANILINE; CALCIUM CHANNEL; CALCIUM CHLORIDE; DIMETHYL SULFOXIDE; DOFETILIDE; LIDOCAINE; SODIUM CALCIUM EXCHANGE PROTEIN; SODIUM CHANNEL; VERAPAMIL; CALCIUM CHANNEL L TYPE; PHENETHYLAMINE DERIVATIVE; POTASSIUM CHANNEL BLOCKING AGENT; SULFONAMIDE;

ACTION POTENTIAL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATRIOVENTRICULAR BLOCK; BREATHING RATE; CALCIUM CURRENT; CONTROLLED STUDY; CORONARY ARTERY BLOOD FLOW; DRUG EFFECT; ELECTROCARDIOGRAM; EXPERIMENTAL RABBIT; FEMALE; HEART ARRHYTHMIA; HEART BEAT; HEART RATE VARIABILITY; HEART REPOLARIZATION; HEART RHYTHM; NONHUMAN; PRIORITY JOURNAL; QRS COMPLEX; QT INTERVAL; QT PROLONGATION; RABBIT; RR INTERVAL; SODIUM CURRENT; TORSADE DES POINTES; ANIMAL; CHEMICALLY INDUCED DISORDER; CHRONIC DISEASE; HEART BLOCK; HEART RATE; IN VITRO STUDY; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; CALCIUM CHANNELS, L-TYPE; CHRONIC DISEASE; CORONARY CIRCULATION; FEMALE; HEART BLOCK; HEART RATE; PHENETHYLAMINES; POTASSIUM CHANNEL BLOCKERS; RABBITS; SODIUM CHANNELS; SODIUM-CALCIUM EXCHANGER; SULFONAMIDES; TORSADES DE POINTES;

EID: 67650591298     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2008.00096.x     Document Type: Article

References (49)

1. Abrahamsson C, Carlsson L, Duker G (1996). Lidocaine and nisoldipine attenuate almokalant-induced dispersion of repolarization and early afterdepolarizations in vitro. J Cardiovasc Electrophysiol 7 : 1074 1081.
2. Acsai K, Kun A, Farkas AS, Fülöp F, Nagy N, Balázs M et al. (2007). Effect of partial blockade of the Na(+)/Ca(2+)-exchanger on Ca(2+) handling in isolated rat ventricular myocytes. Eur J Pharmacol 576 : 1 6.
3. Altman DG (1991). Practical Statistics for Medical Research, 1st edn. Chapman & Hall : London.
4. Amran MS, Hashimoto K, Homma N (2004). Effects of sodium-calcium exchange inhibitors, KB-R7943 and SEA0400, on aconitine-induced arrhythmias in guinea pigs in vivo, in vitro, and in computer simulation studies. J Pharmacol Exp Ther 310 : 83 89.
5. Antzelevitch C, Oliva A (2006). Amplification of spatial dispersion of repolarization underlies sudden cardiac death associated with catecholaminergic polymorphic VT, long QT, short QT and Brugada syndromes. J Intern Med 259 : 48 58.
6. Asano Y, Davidenko JM, Baxter WT, Gray RA, Jalife J (1997). Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart. J Am Coll Cardiol 29 : 831 842.
7. Barrett TD, Hennan JK, Fischbach PS, O'Neill BP, Driscoll EM Jr., Lucchesi BR (2001). Tedisamil and dofetilide-induced torsades de pointes, rate and potassium dependence. Br J Pharmacol 132 : 1493 1500.
8. Batey AJ, Coker SJ (2002). Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes. Br J Pharmacol 135 : 1003 1012.
9. Belardinelli L, Antzelevitch C, Vos MA (2003). Assessing predictors of drug-induced torsade de pointes. Trends Pharmacol Sci 24 : 619 625.
10. Bers DM (2001). Excitation-contraction Coupling and Cardiac Contractile Force, 2nd edn. Kluwer Academic Publishers : Dordrecht.
11. Birinyi P, Acsai K, Bányász T, Tóth A, Horváth B, Virág L et al. (2005). Effects of SEA0400 and KB-R7943 on Na(+)/Ca(2+) exchange current and L-type Ca(2+) current in canine ventricular cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol 372 : 63 70.
12. Burashnikov A, Antzelevitch C (1998). Acceleration-induced action potential prolongation and early afterdepolarizations. J Cardiovasc Electrophysiol 9 : 934 948.
13. Carlsson L, Drews L, Duker G, Schiller-Linhardt G (1993). Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit. J Pharmacol Exp Ther 267 : 1076 1080.
14. Eckardt L, Haverkamp W, Mertens H, Johna R, Clague JR, Borggrefe M et al. (1998). Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin. J Cardiovasc Pharmacol 32 : 425 434.
15. Eckardt L, Breithardt G, Haverkamp W (2002). Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation. J Pharmacol Exp Ther 300 : 64 71.
16. Fabritz L, Kirchhof P, Franz MR, Eckardt L, Monnig G, Milberg P et al. (2003). Prolonged action potential durations, increased dispersion of repolarization, and polymorphic ventricular tachycardia in a mouse model of proarrhythmia. Basic Res Cardiol 98 : 25 32.
17. Farkas A, Curtis MJ (2003). Does QT widening in the Langendorff-perfused rat heart represent the effect of repolarization delay or conduction slowing? J Cardiovasc Pharmacol 42 : 612 621.
18. Farkas A, Batey AJ, Coker SJ (2004). How to measure electrocardiographic QT interval in the anaesthetized rabbit. J Pharmacol Toxicol Methods 50 : 175 185.
19. Farkas AS, Acsai K, Nagy N, Tóth A, Fülöp F, Seprényi G et al. (2008). Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart. Br J Pharmacol 154 : 93 104.
20. Himmel HM (2007). Suitability of commonly used excipients for electrophysiological in-vitro safety pharmacology assessment of effects on hERG potassium current and on rabbit Purkinje fiber action potential. J Pharmacol Toxicol Methods 56 : 145 158.
21. Homma N, Amran MS, Nagasawa Y, Hashimoto K (2006). Topics on the Na+/Ca2+ exchanger: involvement of Na+/Ca2+ exchange system in cardiac triggered activity. J Pharmacol Sci 102 : 17 21.
22. Hondeghem LM, Carlsson L, Duker G (2001). Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation 103 : 2004 2013.
23. Lengyel C, Varró A, Tábori K, Papp JG, Baczkó I (2007). Combined pharmacological block of I(Kr) and I(Ks) increases short-term QT interval variability and provokes torsades de pointes. Br J Pharmacol 151 : 941 951.
24. Matsuda T, Arakawa N, Takuma K, Kishida Y, Kawasaki Y, Sakaue M et al. (2001). SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J Pharmacol Exp Ther 298 : 249 256.
25. Michael G, Dempster J, Kane KA, Coker SJ (2007). Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation. Br J Pharmacol 152 : 1215 1227.
26. Milberg P, Eckardt L, Bruns HJ, Biertz J, Ramtin S, Reinsch N et al. (2002). Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. J Pharmacol Exp Ther 303 : 218 225.
27. Milberg P, Reinsch N, Osada N, Wasmer K, Monnig G, Stypmann J et al. (2005). Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol 100 : 365 371.
28. Nagasawa Y, Zhu BM, Chen J, Kamiya K, Miyamoto S, Hashimoto K (2005). Effects of SEA0400, a Na+/Ca2+ exchange inhibitor, on ventricular arrhythmias in the in vivo dogs. Eur J Pharmacol 506 : 249 255.
29. Nagy ZA, Virág L, Tóth A, Biliczki P, Acsai K, Bányász T et al. (2004). Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed after depolarization in canine heart. Br J Pharmacol 143 : 827 831.
30. Patterson E, Scherlag BJ, Szabo B, Lazzara R (1997). Facilitation of epinephrine-induced afterdepolarizations by class III antiarrhythmic drugs. J Electrocardiol 30 : 217 224.
31. Pinney SP, Koller BS, Franz MR, Woosley RL (1995). Terfenadine increases the QT interval in isolated guinea pig heart. J Cardiovasc Pharmacol 25 : 30 34.
32. Sher AA, Noble PJ, Hinch R, Gavaghan DJ, Noble D (2007). The role of the Na(+)/Ca(2+) exchangers in Ca(2+) dynamics in ventricular myocytes. Prog Biophys Mol Biol 96 : 377 398.
33. Shimizu W, Ohe T, Kurita T, Kawade M, Arakaki Y, Aihara N et al. (1995). Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome. J Am Coll Cardiol 26 : 1299 1309.
34. Shpak B, Gofman Y, Shpak C, Hiller R, Boyman L, Khananshvili D (2006). Effects of purified endogenous inhibitor of the Na+/Ca2+ exchanger on ouabain-induced arrhythmias in the atria and ventricle strips of guinea pig. Eur J Pharmacol 553 : 196 204.
35. Sipido KR, Varró A, Eisner D (2006). Sodium Calcium Exchange as a Target for Antiarrhythmic Therapy, 2006/04/14 edn. Springer-Verlag, Berlin, Heidelberg.
36. Sipido KR, Bito V, Antoons G, Volders PG, Vos MA (2007). Na/Ca exchange and cardiac ventricular arrhythmias. Ann N Y Acad Sci 1099 : 339 348.
37. Szentandrássy N, Birinyi P, Szigeti G, Farkas A, Magyar J, Tóth A et al. (2008). SEA0400 fails to alter the magnitude of intracellular Ca(2+) transients and contractions in Langendorff-perfused guinea pig heart. Naunyn Schmiedebergs Arch Pharmacol 378 : 65 71.
38. Takahashi K, Takahashi T, Suzuki T, Onishi M, Tanaka Y, Hamano-Takahashi A et al. (2003). Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger, on myocardial ischemia-reperfusion injuries. Eur J Pharmacol 458 : 155 162.
39. Tanaka H, Nishimaru K, Aikawa T, Hirayama W, Tanaka Y, Shigenobu K (2002). Effect of SEA0400, a novel inhibitor of sodium-calcium exchanger, on myocardial ionic currents. Br J Pharmacol 135 : 1096 1100.
40. Thomsen MB, Verduyn SC, Stengl M, Beekman JD, de Pater G, van Opstal J et al. (2004). Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation 110 : 2453 2459.
41. Thomsen MB, Matz J, Volders PG, Vos MA (2006). Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias. Pharmacol Ther 112 : 150 170.
42. Tweedie D, O'Gara P, Harding SE, MacLeod KT (1997). The effect of alterations to action potential duration on beta-adrenoceptor-mediated aftercontractions in human and guinea-pig ventricular myocytes. J Mol Cell Cardiol 29 : 1457 1467. (Pubitemid 27259658)
43. Vincze D, Farkas AS, Rudas L, Makra P, Csík N, Leprán I et al. (2008). Relevance of anaesthesia for dofetilide-induced torsades de pointes in alpha1-adrenoceptor-stimulated rabbits. Br J Pharmacol 153 : 75 89.
44. Volders PG, Vos MA, Szabo B, Sipido KR, de Groot SH, Gorgels AP et al. (2000). Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts. Cardiovasc Res 46 : 376 392.
45. Volders PG, Kulcsar A, Vos MA, Sipido KR, Wellens HJ, Lazzara R et al. (1997). Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res 34 : 348 359.
46. Watano T, Harada Y, Harada K, Nishimura N (1999). Effect of Na+/Ca2+ exchange inhibitor, KB-R7943 on ouabain-induced arrhythmias in guinea-pigs. Br J Pharmacol 127 : 1846 1850.
47. Yang T, Snyders D, Roden DM (2001). Drug block of I(kr): model systems and relevance to human arrhythmias. J Cardiovasc Pharmacol 38 : 737 744.
48. Zabel M, Hohnloser SH, Behrens S, Li YG, Woosley RL, Franz MR (1997). Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model. J Cardiovasc Electrophysiol 8 : 1148 1158.
49. Zygmunt AC, Goodrow RJ, Antzelevitch C (2000). I(NaCa) contributes to electrical heterogeneity within the canine ventricle. Am J Physiol Heart Circ Physiol 278 : H1671 H1678.