Analysis of Unipolar Electrograms in Rabbit Heart Demonstrated the Key Role of Ventricular Apicobasal Dispersion in Arrhythmogenicity

Cardiovascular Toxicology

Volumn 14, Issue 4, 2014, Pages 316-328

  Guérard, Nicolas ^a   Jordaan, Pierre ^a   Dumotier, Bérengère ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Apex to base dispersion of repolarization; Arrhythmogenicity; Rabbit heart; Repolarization reserve; Torsade de Pointes; Transmural

Indexed keywords

6-CYANO-4-(N-ETHYLSULFONYL-N-METHYLAMINO)-3-HYDROXY-2,2-DIMETHYLCHROMANE; ANTIARRHYTHMIC AGENT; ANTIOXIDANT; CHROMAN DERIVATIVE; QUINIDINE; SOTALOL; SULFONAMIDE;

ANIMAL; ARRHYTHMIAS, CARDIAC; ENDOCARDIUM; HEART FUNCTION TEST; METABOLISM; PATHOPHYSIOLOGY; PERICARDIUM; RABBIT; TORSADES DE POINTES;

ANIMALS; ANTI-ARRHYTHMIA AGENTS; ANTIOXIDANTS; ARRHYTHMIAS, CARDIAC; CHROMANS; ELECTROPHYSIOLOGIC TECHNIQUES, CARDIAC; ENDOCARDIUM; PERICARDIUM; QUINIDINE; RABBITS; SOTALOL; SULFONAMIDES; TORSADES DE POINTES;

EID: 84936748697     PISSN: 15307905     EISSN: 15590259     Source Type: Journal    
DOI: 10.1007/s12012-014-9254-2     Document Type: Article

References (40)

1. Dessertenne, F. (1966). Ventricular tachycardia with two variable opposing foci. Archives des Maladies du Coeur et des Vaisseaux,59, 263–272.
2. Hondeghem, L. M. (2008). QT and TdP—QT: An unreliable predictor of proarrhythmia. Acta Cardiologica,63, 1–7.
3. Shah, R. R., & Hondeghem, L. M. (2005). Refining detection of drug-induced proarrhythmia: QT interval and TRIaD. Heart Rhythm,2, 758–772.
4. Yan, G. X., Shimizu, W., & Antzelevitch, C. (1998). Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations. Circulation,98, 1921–1927.
5. Chen, X., Cordes, J. S., Bradley, J. A., Sun, Z., & Zhou, J. (2006). Use of arterially perfused rabbit ventricular wedge in predicting arrhythmogenic potentials of drugs. Journal of Pharmacological and Toxicological Methods,54, 261–272.
6. Emori, T., & Antzelevitch, C. (2001). Cellular basis for complex T waves and arrhythmic activity following combined I-Kr and I-Ks block. Journal of Cardiovascular Electrophysiology,12, 1369–1378.
7. Extramiana, F., & Antzelevitch, C. (2004). Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome. Circulation,110, 3661–3666.
8. Yan, G. X., Wu, Y., Liu, T. X., Wang, J. X., Marinchak, R. A., & Kowey, P. R. (2001). Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome—Direct evidence from intracellular recordings in the intact left ventricular wall. Circulation,103, 2851–2856.
9. Wang, D., Patel, C., Cui, C., & Yan, G. X. (2008). Preclinical assessment of drug-induced proarrhythmias: Role of the arterially perfused rabbit left ventricular wedge preparation. Pharmacology & Therapeutics,119, 141–151.
10. Voss, F., Opthof, T., Marker, J., Bauer, A., Katus, H. A., & Becker, R. (2009). There is no transmural heterogeneity in an index of action potential duration in the canine left ventricle. Heart Rhythm,6, 1028–1034.
11. Taggart, P., Sutton, P. M. I., Opthof, T., Coronel, R., Trimlett, R., Pugsley, W., et al. (2001). Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia. Cardiovascular Research,50, 454–462.
12. Conrath, C. E., Wilders, R., Coronel, R., de Bakker, J. M. T., Taggart, P., de Groot, J. R., et al. (2004). Intercellular coupling through gap junctions masks M cells in the human heart. Cardiovascular Research,62, 407–414.
13. Opthof, T., Coronel, R., Janse, M. J., & Rosen, M. R. (2007). A wedge is not a heart. Heart Rhythm,4(8), 1116–1119.
14. Pak, H. N., Hong, S. J., Hwang, G. S., Lee, H. S., Park, S. W., Ahn, J. C., et al. (2004). Spatial dispersion of action potential duration restitution kinetics is associated with induction of ventricular tachycardia/fibrillation in humans. Journal of Cardiovascular Electrophysiology,15, 1357–1363.
15. Sims, C., Reisenweber, S., Viswanathan, P. C., Choi, B. R., Walker, W. H., & Salama, G. (2008). Sex, age, and regional differences in L-type calcium current are important determinants of arrhythmia phenotype in rabbit hearts with drug-induced long QT type 2. Circulation Research,102, E86–E100.
16. Szentadrassy, N., Banyasz, T., Biro, T., Szabo, G., Toth, B. I., Magyar, J., et al. (2005). Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium. Cardiovascular Research,65, 851–860.
17. Cheng, J. H., & Kodama, I. (2004). Two components of delayed rectifier K+ current in heart: Molecular basis, functional diversity, and contribution to repolarization. Acta Pharmacologica Sinica,25, 137–145.
18. Thomsen, M. B., Volders, P. G. A., Beekman, J. D. M., Matz, J., & Vos, M. A. (2006). Beat-to-beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced Torsades de pointes. Journal of the American College of Cardiology,48(6), 1268–1276.
19. Guerard, N. C., Traebert, M., Suter, W., & Dumotier, B. M. (2008). Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. Journal of Pharmacological and Toxicological Methods,58, 32–40.
20. Redfern, W. S., Carlsson, L., Davis, A. S., Lynch, W. G., MacKenzie, I., Palethorpe, S., et al. (2003). Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: Evidence for a provisional safety margin in drug development. Cardiovascular Research,58, 32–45.
21. Hohnloser, S. H., & Woosley, R. L. (1994). Drug-therapy—Sotalol. New England Journal of Medicine,331, 31–38.
22. Roden, D. M., Woosley, R. L., & Primm, R. K. (1986). Incidence and clinical features of the quinidine-associated long QT syndrome: Implications for patient care. American Heart Journal,111, 1088–1093.
23. Pugsley, M. K., Walker, M. J., & Saint, D. A. (2005). Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine. Clinical and Experimental Pharmacology and Physiology,32, 60–65.
24. Bosch, R. F., Gaspo, R., Busch, A. E., Lang, H. J., Li, G. R., & Nattel, S. (1998). Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes. Cardiovascular Research,38, 441–450.
25. Roden, D. M., & Yang, T. (2005). Protecting the heart against arrhythmias: Potassium current physiology and repolarization reserve. Circulation,112, 1376–1378.
26. Coronel, R., de Bakker, J. M., Wilms-Schopman, F. J., Opthof, T., Linnenbank, A. C., Belterman, C. N., et al. (2006). Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: Experimental evidence to resolve some controversies. Heart Rhythm,3, 1043–1050.
27. Haws, C. W., & Lux, R. L. (1990). Correlation between invivo transmembrane action-potential durations and activation-recovery intervals from electrograms—Effects of interventions that alter repolarization time. Circulation,81, 281–288.
28. Janse, M. J., Coronel, R., Opthof, T., Sosunov, E. A., Anyukhovsky, E. P., & Rosen, M. R. (2012). Repolarization gradients in the intact heart: Transmural or apico-basal? Progress in Biophysics and Molecular Biology,109, 6–15.
29. Brunner, M., Peng, X. W., Liu, G. X., Ren, X. Q., Ziv, O., Choi, B. R., et al. (2008). Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. Journal of Clinical Investigation,118, 2246–2259.
30. Ather, S., & Wehrens, X. (2013). CA2+ release channels (ryanodine receptors) and arrhythmogenesis. Electrical Diseases of the Heart,1, 281–297.
31. Burashnikov, A., Mannava, S., & Antzelevitch, C. (2004). Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium: Effect of I-Kr and I-Kur/I-to block. American Journal of Physiology-Heart and Circulatory Physiology,286, H2393–H2400.
32. El-Sherif, N., Caref, E. B., Yin, H., & Restivo, M. (1996). The electrophysiological mechanism of ventricular arrhythmias in the long QT syndrome: Tridimensional mapping of activation and recovery patterns. Circulation Research,79, 474–492.
33. Weissenburger, J., Nesterenko, V. V., & Antzelevitch, C. (2000). Transmural heterogeneity of ventricular repolarization under baseline and long QT conditions in the canine heart in vivo: Torsades de Pointes develops with halothane but not pentobarbital anesthesia. Journal of Cardiovascular Electrophysiology,11, 290–304.
34. Drouin, E., Charpentier, F., Gauthier, C., Laurent, K., & Lemarec, H. (1995). Electrophysiologic characteristics of cells spanning the left-ventricular wall of human heart—Evidence for presence of M-Cells. Journal of the American College of Cardiology,26, 185–192.
35. Yan, G. X., Rials, S. J., Wu, Y., Liu, T. X., Xu, X. P., Marinchak, R. A., et al. (2001). Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization. American Journal of Physiology-Heart and Circulatory Physiology,281, H1968–H1975.
36. Bauer, A., Becker, R., Freigang, K. D., Senges, J. C., Voss, F., Hansen, A., et al. (1999). Rate- and site-dependent effects of propafenone, dofetilide and the new I-Ks-blocking agent chromanol 293b on individual muscle layers of the intact canine heart. Circulation,100, 2184–2190.
37. RodriguezSinovas, A., Cinca, J., Tapias, A., Armadans, L., Tresanchez, M., & SolerSoler, J. (1997). Lack of evidence of M-cells in porcine left ventricular myocardium. Cardiovascular Research,33, 307–313.
38. Yamaguchi, M., Shimizu, M., Ino, H., Terai, H., Uchiyama, K., Oe, K., et al. (2003). T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: A new index for arrhythmogenicity. Clinical Science,105, 671–676.
39. Lubinski, A., Lewicka-Nowak, E., Kempa, M., Baczynska, A. M., Romanowska, I., & Swiatecka, G. (1998). New insight into repolarization abnormalities in patients with congenital long QT syndrome: The increased transmural dispersion of repolarization. Pacing and Clinical Electrophysiology,21, 172–175.
40. Smetana, P., Schmidt, A., Zabel, M., Hnatkova, K., Franz, M., Huber, K., et al. (2005). Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: Peak to the end of the T wave interval and nondipolar repolarization components. Journal of Electrocardiology,44, 301–308.