Heart Rhythm
Volume 7, Issue 6 , Pages 820-827 , June 2010

Genotype-phenotype correlation in tissue models of Brugada syndrome simulating patients with sodium and calcium channelopathies

  • Hiroshi Morita, MD

      Affiliations

    • Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana
    • Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    • ,
  • Douglas P. Zipes, MD, FHRS

      Affiliations

    • Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana
    • ,
  • Shiho T. Morita, MD

      Affiliations

    • Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana
    • Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    • ,
  • Jiashin Wu, PhD

      Affiliations

    • Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida
    • Corresponding Author InformationAddress reprint requests and correspondence: Jiashin Wu, Department of Molecular Pharmacology and Physiology, University of South Florida, 4001 East Fletcher Avenue, Tampa, Florida 33612

Received 24 August 2009 ,Accepted 25 January 2010.

References 

  1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992;20:1391–1396
  2. Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J. 1989;118:1203–1209
  3. Chen Q, Kirsch GE, Zhang D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998;392:293–296
  4. London B, Michalec M, Mehdi H, et al. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation. 2007;116:2260–2268
  5. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007;115:442–449
  6. Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet. 2008;372:750–763
  7. Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA. 2004;292:1341–1344
  8. 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;103:89–95
  9. Zhang L, Timothy KW, Vincent GM, et al. Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes. Circulation. 2000;102:2849–2855
  10. Shimizu W. The long QT syndrome: therapeutic implications of a genetic diagnosis. Cardiovasc Res. 2005;67:347–356
  11. Smits JP, Eckardt L, Probst V, et al. Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol. 2002;40:350–356
  12. Yokokawa M, Noda T, Okamura H, et al. Comparison of long-term follow-up of electrocardiographic features in Brugada syndrome between the SCN5A-positive probands and the SCN5A-negative probands. Am J Cardiol. 2007;100:649–655
  13. Morita H, Nagase S, Miura D, et al. Differential effects of cardiac sodium channel mutations on initiation of ventricular arrhythmias in patients with Brugada syndrome. Heart Rhythm. 2009;6:487–492
  14. Morita H, Zipes DP, Morita ST, Lopshire JC, Wu J. Epicardial ablation eliminates ventricular arrhythmias in an experimental model of Brugada syndrome. Heart Rhythm. 2009;6:665–671
  15. Wu J, Biermann M, Rubart M, Zipes DP. Cytochalasin D as excitation-contraction uncoupler for optically mapping action potentials in wedges of ventricular myocardium. J Cardiovasc Electrophysiol. 1998;9:1336–1347
  16. Morita H, Kusano KF, Miura D, et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation. 2008;118:1697–1704
  17. Morita H, Zipes DP, Morita ST, Wu J. Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome. Heart Rhythm. 2007;4:188–197
  18. Fish JM, Antzelevitch C. Role of sodium and calcium channel block in unmasking the Brugada syndrome. Heart Rhythm. 2004;1:210–217
  19. Fish JM, Antzelevitch C. Cellular mechanism and arrhythmogenic potential of T-wave alternans in the Brugada syndrome. J Cardiovasc Electrophysiol. 2008;19:301–308
  20. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005;2:429–440
  21. Shimizu W, Aiba T, Kamakura S. Mechanisms of disease: current understanding and future challenges in Brugada syndrome. Nat Clin Pract Cardiovasc Med. 2005;2:408–414
  22. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation. 1999;100:1660–1666
  23. Aiba T, Shimizu W, Hidaka I, et al. Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model: high-resolution optical mapping study. J Am Coll Cardiol. 2006;47:2074–2085
  24. Morita H, Zipes DP, Fukushima-Kusano K, et al. Repolarization heterogeneity in the right ventricular outflow tract: correlation with ventricular arrhythmias in Brugada patients and in an in vitro canine Brugada model. Heart Rhythm. 2008;5:725–733
  25. Morita H, Zipes DP, Lopshire J, et al. T wave alternans in an in vitro canine tissue model of Brugada syndrome. Am J Physiol Heart Circ Physiol. 2006;291:H421–H428
  26. Fish JM, Welchons DR, Kim YS, et al. Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome. Circulation. 2006;113:1393–1400
  27. Yasuda M, Nakazato Y, Yamashita H, et al. ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs. Heart. 2001;85:E3
  28. Hisamatsu K, Kusano KF, Morita H, et al. Relationships between depolarization abnormality and repolarization abnormality in patients with Brugada syndrome: using body surface signal-averaged electrocardiography and body surface maps. J Cardiovasc Electrophysiol. 2004;15:870–876
  29. Morita H, Zipes DP, Morita ST, Wu J. Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome. Heart Rhythm. 2007;4:66–74
  30. Antzelevitch C, Fish J. Electrical heterogeneity within the ventricular wall. Basic Res Cardiol. 2001;96:517–527
  31. Di Diego JM, Cordeiro JM, Goodrow RJ, et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation. 2002;106:2004–2011
  32. Yan GX, Kowey PR. ST segment elevation and sudden cardiac death: from the Brugada syndrome to acute myocardial ischemia. J Cardiovasc Electrophysiol. 2000;11:1330–1332
  33. Shimizu W, Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of beta-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes. Circulation. 1998;98:2314–2322
  34. Shimizu W, Antzelevitch C. Differential response of transmural dispersion of repolarization and torsade de pointes to beta-adrenergic agonists and antagonists in three models of the long QT syndrome. J Electrocardiol. 1999;32(Suppl):150
  35. Morita ST, Zipes DP, Morita H, Wu J. Analysis of action potentials in the canine ventricular septum: no phenotypic expression of M cells. Cardiovasc Res. 2007;74:96–103
  36. Fujimoto Y, Kusano KF, Morita H, et al. Nicorandil attenuates both temporal and spatial repolarization alternans. J Electrocardiol. 2000;33:269–277
  37. Cordeiro JM, Greene L, Heilmann C, et al. Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle. Am J Physiol Heart Circ Physiol. 2004;286:H1471–H1479
  38. Greenstein JL, Wu R, Po S, et al. Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration. Circ Res. 2000;87:1026–1033
  39. Sun X, Wang HS. Role of the transient outward current (Ito) in shaping canine ventricular action potential—a dynamic clamp study. J Physiol. 2005;564:411–419
  40. Yeola SW, Snyders DJ. Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current. Cardiovasc Res. 1997;33:540–547
  41. Katsube Y, Yokoshiki H, Nguyen L, Sperelakis N. Differences in isoproterenol stimulation of Ca2+ current of rat ventricular myocytes in neonatal compared to adult. Eur J Pharmacol. 1996;317:391–400

 Dr. Zipes is a grantee and consultant for Medtronic, Inc.

 This study was partially supported by American Heart Association grant no. 455517Z (to JW). The manuscript was processed by a Guest Editor.

PII: S1547-5271(10)00070-6

doi: 10.1016/j.hrthm.2010.01.039

Heart Rhythm
Volume 7, Issue 6 , Pages 820-827 , June 2010

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