Skip to main content
SpringerLink
Log in

Ionic and Cellular Basis for Arrhythmogenesis

  • Chapter
  • First Online:
Management of Cardiac Arrhythmias

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Recent years have witnessed important advances in our appreciation of the mechanisms underlying the development of cardiac arrhythmias. Our understanding of these phenomena has been fueled by innovative advances in the genetic, ionic, and cellular basis for electrical disturbances of the heart. This chapter focuses on our present understanding of ionic and cellular mechanisms responsible for common cardiac arrhythmias. The mechanisms responsible for cardiac arrhythmias are divided into two major categories: (1) enhanced or abnormal impulse formation and (2) reentry, which occurs when a propagating impulse fails to die out after normal activation of the heart and persists to re-excite the heart after expiration of the refractory period.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mines GR (1914) Further experiments on the action of the vagus on the electrogram of the frog’s heart. J Physiol 47(6):419–430

    PubMed  CAS  Google Scholar 

  2. Moe GK (1975) Evidence for reentry as a mechanism of cardiac arrhythmias. Rev Physiol Biochem Pharmacol 72:55–81

    PubMed  CAS  Google Scholar 

  3. Hoffman BF, Dangman KH (1987) Mechanisms for cardiac arrhythmias. Experientia 43(10):1049–1056

    PubMed  CAS  Google Scholar 

  4. Lazzara R (1988) Electrophysiological mechanisms for ventricular arrhythmias. Clin Cardiol 11(3 Suppl 2):II1–II4

    PubMed  CAS  Google Scholar 

  5. Lukas A, Antzelevitch C (1996) Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia. Cardiovasc Res 32(3):593–603

    PubMed  CAS  Google Scholar 

  6. Yan GX, Antzelevitch C (1999) Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 100(15):1660–1666

    PubMed  CAS  Google Scholar 

  7. Antzelevitch C (2005) In vivo human demonstration of phase 2 reentry. Heart Rhythm 2(8):804–806

    PubMed  Google Scholar 

  8. Yan GX, Joshi A, Guo D, Hlaing T, Martin J, Xu X et al (2004) Phase 2 reentry as a trigger to initiate ventricular fibrillation during early acute myocardial ischemia. Circulation 110(9):1036–1041

    PubMed  Google Scholar 

  9. Jalife J (2003) Rotors and spiral waves in atrial fibrillation. J Cardiovasc Electrophysiol 14(7):776–780

    PubMed  Google Scholar 

  10. Guo D, Zhou J, Zhao X, Gupta P, Kowey PR, Martin J et al (2008) L-type calcium current recovery versus ventricular repolarization: preserved membrane-stabilizing mechanism for different QT intervals across species. Heart Rhythm 5(2):271–279

    PubMed  Google Scholar 

  11. Burashnikov A, Antzelevitch C (2003) Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity. Circulation 107(18):2355–2360

    PubMed  Google Scholar 

  12. Burashnikov A, Antzelevitch C (2006) Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation. Pacing Clin Electrophysiol 29(3):290–295

    PubMed  Google Scholar 

  13. Patterson E, Lazzara R, Szabo B, Liu H, Tang D, Li YH et al (2006) Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins. J Am Coll Cardiol 47(6):1196–1206

    PubMed  CAS  Google Scholar 

  14. Vassalle M (1977) Cardiac automaticity and its control. Am J Physiol 233(6):H625–H634

    PubMed  CAS  Google Scholar 

  15. Glitsch HG (1979) Characteristics of active Na transport in intact cardiac cells. Am J Physiol 236(2):H189–H199

    PubMed  CAS  Google Scholar 

  16. Gadsby DC, Cranefield PF (1979) Direct measurement of changes in sodium pump current in canine cardiac Purkinje fibers. Proc Natl Acad Sci USA 76(4):1783–1787

    PubMed  CAS  Google Scholar 

  17. DiFrancesco D (1985) The cardiac hyperpolarizing-activated current, if. Origins and developments. Prog Biophys Mol Biol 46(3):163–183

    PubMed  CAS  Google Scholar 

  18. DiFrancesco D (1995) The pacemaker current (I(f)) plays an important role in regulating SA node pacemaker activity. Cardiovasc Res 30(2):307–308

    PubMed  CAS  Google Scholar 

  19. Satoh H, Hashimoto K (1984) Effect of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212) on the membrane currents of rabbit sino-atrial node cells. Arzneimittelforschung 34(3A):376–380

    PubMed  CAS  Google Scholar 

  20. Vassalle M, Yu H, Cohen IS (1995) The pacemaker current in cardiac Purkinje myocytes. J Gen Physiol 106(3):559–578

    PubMed  CAS  Google Scholar 

  21. Soejima M, Noma A (1984) Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch 400(4):424–431

    PubMed  CAS  Google Scholar 

  22. DiFrancesco D, Tromba C (1988) Inhibition of the hyperpolarization-activated current (if) induced by acetylcholine in rabbit sino-atrial node myocytes. J Physiol 405:477–491

    PubMed  CAS  Google Scholar 

  23. Katzung BG, Hondeghem LM, Grant AO (1975) Letter: cardiac ventricular automaticity induced by current of injury. Pflugers Arch 360(2):193–197

    PubMed  CAS  Google Scholar 

  24. Janse MJ, Wilms-Schopman F (1982) Effect of changes in perfusion pressure on the position of the electrophysiologic border zone in acute regional ischemia in isolated perfused dog and pig hearts. Am J Cardiol 50(1):74–82

    PubMed  CAS  Google Scholar 

  25. Winum PF, Cayla G, Rubini M, Beck L, Messner-Pellenc P (2009) A case of cardiomyopathy induced by inappropriate sinus tachycardia and cured by ivabradine. Pacing Clin Electrophysiol 32(7):942–944

    PubMed  Google Scholar 

  26. Vermeulen JT, McGuire MA, Opthof T, Coronel R, de Bakker JM, Klopping C et al (1994) Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res 28(10):1547–1554

    PubMed  CAS  Google Scholar 

  27. Nuss HB, Kaab S, Kass DA, Tomaselli GF, Marban E (1999) Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure. Am J Physiol 277(1 Pt 2):H80–H91

    PubMed  CAS  Google Scholar 

  28. Hoppe UC, Jansen E, Sudkamp M, Beuckelmann DJ (1998) Hyperpolarization-activated inward current in ventricular myocytes from normal and failing human hearts. Circulation 97(1):55–65

    PubMed  CAS  Google Scholar 

  29. Cerbai E, Barbieri M, Mugelli A (1996) Occurrence and properties of the hyperpolarization-activated current If in ventricular myocytes from normotensive and hypertensive rats during aging. Circulation 94(7):1674–1681

    PubMed  CAS  Google Scholar 

  30. Hauswirth O, Noble D, Tsien RW (1969) The mechanism of oscillatory activity at low membrane potentials in cardiac Purkinje fibres. J Physiol 200(1):255–265

    PubMed  CAS  Google Scholar 

  31. Imanishi S, Surawicz B (1976) Automatic activity in depolarized guinea pig ventricular myocardium. Characteristics and mechanisms. Circ Res 39(6):751–759

    PubMed  CAS  Google Scholar 

  32. Dangman KH, Hoffman BF (1983) Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: suppression of automaticity and abolition of triggering. J Pharmacol Exp Ther 227(3):578–586

    PubMed  CAS  Google Scholar 

  33. Rota M, Vassalle M (2003) Patch-clamp analysis in canine cardiac Purkinje cells of a novel sodium component in the pacemaker range. J Physiol 548(Pt 1):147–165

    PubMed  CAS  Google Scholar 

  34. Katzung BG, Morgenstern JA (1977) Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ Res 40(1):105–111

    PubMed  CAS  Google Scholar 

  35. Pappano AJ, Carmeliet EE (1979) Epinephrine and the pacemaking mechanism at plateau potentials in sheep cardiac Purkinje fibers. Pflugers Arch 382(1):17–26

    PubMed  CAS  Google Scholar 

  36. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G et al (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339(10):659–666

    PubMed  CAS  Google Scholar 

  37. Lai LP, Su MJ, Lin JL, Tsai CH, Lin FY, Chen YS et al (1999) Measurement of funny current (I(f)) channel mRNA in human atrial tissue: correlation with left atrial filling pressure and atrial fibrillation. J Cardiovasc Electrophysiol 10(7):947–953

    PubMed  CAS  Google Scholar 

  38. Yan GX, Wu Y, Liu T, Wang J, Marinchak RA, Kowey PR (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(23):2851–2856

    PubMed  CAS  Google Scholar 

  39. Adamantidis MM, Caron JF, Dupuis BA (1986) Triggered activity induced by combined mild hypoxia and acidosis in guinea-pig Purkinje fibers. J Mol Cell Cardiol 18(12):1287–1299

    PubMed  CAS  Google Scholar 

  40. Priori SG, Corr PB (1990) Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines. Am J Physiol 258(6 Pt 2):H1796–H1805

    PubMed  CAS  Google Scholar 

  41. 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(2):348–359

    PubMed  CAS  Google Scholar 

  42. Liu T, Brown BS, Wu Y, Antzelevitch C, Kowey PR, Yan GX (2006) Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias. Heart Rhythm 3(8):948–956

    PubMed  Google Scholar 

  43. Volders PG, Sipido KR, Vos MA, Kulcsar A, Verduyn SC, Wellens HJ (1998) Cellular basis of biventricular hypertrophy and arrhythmogenesis in dogs with chronic complete atrioventricular block and acquired Torsade de Pointes. Circulation 98(11):1136–1147

    PubMed  CAS  Google Scholar 

  44. Yan GX, Rials SJ, Wu Y, Liu T, Xu X, Marinchak RA et al (2001) Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization. Am J Physiol Heart Circ Physiol 281(5):H1968–H1975

    PubMed  CAS  Google Scholar 

  45. Roden DM (1986) Pharmacologic information required for design of programmed electrical stimulation protocols. Circulation 73(2 Pt 2):II39–II44

    PubMed  CAS  Google Scholar 

  46. Davidenko JM, Cohen L, Goodrow R, Antzelevitch C (1989) Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium. Circulation 79(3):674–686

    PubMed  CAS  Google Scholar 

  47. Sicouri S, Antzelevitch C (1991) Afterdepolarizations and triggered activity develop in a select population of cells (M cells) in canine ventricular myocardium: the effects of acetylstrophanthidin and Bay K 8644. Pacing Clin Electrophysiol 14(11 Pt 2):1714–1720

    PubMed  CAS  Google Scholar 

  48. Liu DW, Antzelevitch C (1995) Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. Circ Res 76(3):351–365

    PubMed  CAS  Google Scholar 

  49. Burashnikov A, Antzelevitch C (2002) Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations. J Cardiovasc Electrophysiol 13(2):172–177

    PubMed  Google Scholar 

  50. Yan GX, Rials SJ, Wu Y, Liu T, Xu X, Marinchak RA et al (2001) Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization. Am J Physiol Heart Circ Physiol 281(5):H1968–H1975

    PubMed  CAS  Google Scholar 

  51. Xu X, Rials SJ, Wu Y, Salata JJ, Liu T, Bharucha DB et al (2001) Left ventricular hypertrophy decreases slowly but not rapidly activating delayed rectifier potassium currents of epicardial and endocardial myocytes in rabbits. Circulation 103(11):1585–1590

    PubMed  CAS  Google Scholar 

  52. Valdivia CR, Chu WW, Pu J, Foell JD, Haworth RA, Wolff MR et al (2005) Increased late sodium current in myocytes from a canine heart failure model and from failing human heart. J Mol Cell Cardiol 38(3):475–483

    PubMed  CAS  Google Scholar 

  53. Belardinelli L, Antzelevitch C, Vos MA (2003) Assessing predictors of drug-induced Torsade de Pointes. Trends Pharmacol Sci 24(12):619–625

    PubMed  CAS  Google Scholar 

  54. Lankipalli RS, Zhu T, Guo D, Yan GX (2005) Mechanisms underlying arrhythmogenesis in long QT syndrome. J Electrocardiol 38(4 Suppl):69–73

    PubMed  Google Scholar 

  55. Viswanathan PC, Rudy Y (1999) Pause induced early afterdepolarizations in the long QT syndrome: a simulation study. Cardiovasc Res 42(2):530–542

    PubMed  CAS  Google Scholar 

  56. Guo D, Zhao X, Wu Y, Liu T, Kowey PR, Yan GX (2007) L-type calcium current reactivation contributes to arrhythmogenesis associated with action potential triangulation. J Cardiovasc Electrophysiol 18(2):196–203

    PubMed  Google Scholar 

  57. Hondeghem LM, Lu HR, van Rossem K, De Clerck F (2003) Detection of proarrhythmia in the female rabbit heart: blinded validation. J Cardiovasc Electrophysiol 14(3):287–294

    PubMed  Google Scholar 

  58. Antzelevitch C, Sun ZQ, Zhang ZQ, Yan GX (1996) Cellular and ionic mechanisms underlying erythromycin-induced long QT intervals and Torsade de Pointes. J Am Coll Cardiol 28(7):1836–1848

    PubMed  CAS  Google Scholar 

  59. Antzelevitch C, Belardinelli L (2006) The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis. J Cardiovasc Electrophysiol 17(Suppl 1):S79–S85

    PubMed  Google Scholar 

  60. Kass RS, Tsien RW, Weingart R (1978) Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol 281:209–226

    PubMed  CAS  Google Scholar 

  61. Cannell MB, Lederer WJ (1986) The arrhythmogenic current ITI in the absence of electrogenic sodium-calcium exchange in sheep cardiac Purkinje fibres. J Physiol 374:201–219

    PubMed  CAS  Google Scholar 

  62. Fedida D, Noble D, Shimoni Y, Spindler AJ (1987) Inward current related to contraction in guinea-pig ventricular myocytes. J Physiol 385:565–589

    PubMed  CAS  Google Scholar 

  63. Laflamme MA, Becker PL (1996) Ca2+-induced current oscillations in rabbit ventricular myocytes. Circ Res 78(4):707–716

    PubMed  CAS  Google Scholar 

  64. Zygmunt AC, Goodrow RJ, Weigel CM (1998) INaCa and ICl(Ca) contribute to isoproterenol-induced delayed after depolarizations in midmyocardial cells. Am J Physiol 275(6 Pt 2):H1979–H1992

    PubMed  CAS  Google Scholar 

  65. Aronson RS (1981) Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension. Circ Res 48(5):720–727

    PubMed  CAS  Google Scholar 

  66. Lazzara R, el Sherif N, Scherlag BJ (1973) Electrophysiological properties of canine Purkinje cells in one-day-old myocardial infarction. Circ Res 33(6):722–734

    PubMed  CAS  Google Scholar 

  67. Pogwizd SM, Onufer JR, Kramer JB, Sobel BE, Corr PB (1986) Induction of delayed afterdepolarizations and triggered activity in canine Purkinje fibers by lysophosphoglycerides. Circ Res 59(4):416–426

    PubMed  CAS  Google Scholar 

  68. Song Y, Belardinelli L (1994) ATP promotes development of afterdepolarizations and triggered activity in cardiac myocytes. Am J Physiol 267(5 Pt 2):H2005–H2011

    PubMed  CAS  Google Scholar 

  69. Caroni P, Villani F, Carafoli E (1981) The cardiotoxic antibiotic doxorubicin inhibits the Na+/Ca2+ exchange of dog heart sarcolemmal vesicles. FEBS Lett 130(2):184–186

    PubMed  CAS  Google Scholar 

  70. Spinelli W, Sorota S, Siegal M, Hoffman BF (1991) Antiarrhythmic actions of the ATP-regulated K+ current activated by pinacidil. Circ Res 68(4):1127–1137

    PubMed  CAS  Google Scholar 

  71. So HS, Park C, Kim HJ, Lee JH, Park SY, Lee JH et al (2005) Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells. Hear Res 204(1–2):127–139

    PubMed  CAS  Google Scholar 

  72. Chattipakorn N, Ideker RE (2003) Delayed afterdepolarization inhibitor: a potential pharmacologic intervention to improve defibrillation efficacy. J Cardiovasc Electrophysiol 14(1):72–75

    PubMed  Google Scholar 

  73. Letienne R, Vie B, Puech A, Vieu S, Le Grand B, John GW (2001) Evidence that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the cat cardiovascular system. Naunyn Schmiedebergs Arch Pharmacol 363(4):464–471

    PubMed  CAS  Google Scholar 

  74. Antzelevitch C, Belardinelli L, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM et al (2004) Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 110(8):904–910

    PubMed  CAS  Google Scholar 

  75. Song Y, Shryock JC, Wu L, Belardinelli L (2004) Antagonism by ranolazine of the pro-arrhythmic effects of increasing late INa in guinea pig ventricular myocytes. J Cardiovasc Pharmacol 44(2):192–199

    PubMed  CAS  Google Scholar 

  76. Ritchie AH, Kerr CR, Qi A, Yeung-Lai-Wah JA (1989) Nonsustained ventricular tachycardia arising from the right ventricular outflow tract. Am J Cardiol 64(10):594–598

    PubMed  CAS  Google Scholar 

  77. Wilber DJ, Davis MJ, Rosenbaum M, Ruskin JN, Garan H (1987) Incidence and determinants of multiple morphologically distinct sustained ventricular tachycardias. J Am Coll Cardiol 10(3):583–591

    PubMed  CAS  Google Scholar 

  78. Cardinal R, Scherlag BJ, Vermeulen M, Armour JA (1992) Distinct activation patterns of idioventricular rhythms and sympathetically-induced ventricular tachycardias in dogs with atrioventricular block. Pacing Clin Electrophysiol 15(9):1300–1316

    PubMed  CAS  Google Scholar 

  79. Lerman BB, Belardinelli L, West GA, Berne RM, DiMarco JP (1986) Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity. Circulation 74(2):270–280

    PubMed  CAS  Google Scholar 

  80. Lerman BB, Stein K, Engelstein ED, Battleman DS, Lippman N, Bei D et al (1995) Mechanism of repetitive monomorphic ventricular tachycardia. Circulation 92(3):421–429

    PubMed  CAS  Google Scholar 

  81. Pogwizd SM, McKenzie JP, Cain ME (1998) Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. Circulation 98(22):2404–2414

    PubMed  CAS  Google Scholar 

  82. Leenhardt A, Thomas O, Cauchemez B, Maison-Blanche P, Denjoy I, de Jode P et al (1995) Value of the exercise test in the study of arrhythmia. Arch Mal Coeur Vaiss 88(Spec No 1):59–66

    PubMed  Google Scholar 

  83. Swan H, Piippo K, Viitasalo M, Heikkila P, Paavonen T, Kainulainen K et al (1999) Arrhythmic disorder mapped to chromosome 1q42–q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J Am Coll Cardiol 34(7):2035–2042

    PubMed  CAS  Google Scholar 

  84. Priori SG, Napolitano C (2002) Genetic defects of cardiac ion channels. The hidden substrate for Torsades de Pointes. Cardiovasc Drugs Ther 16(2):89–92

    PubMed  CAS  Google Scholar 

  85. Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R et al (2001) Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103(2):196–200

    PubMed  CAS  Google Scholar 

  86. Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbhatt B et al (2001) Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103(4):485–490

    PubMed  CAS  Google Scholar 

  87. Nam GB, Burashnikov A, Antzelevitch C (2005) Cellular mechanisms underlying the development of catecholaminergic ventricular tachycardia. Circulation 111(21):2727–2733

    PubMed  Google Scholar 

  88. 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(3):376–392

    PubMed  CAS  Google Scholar 

  89. Patterson E, Po SS, Scherlag BJ, Lazzara R (2005) Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation. Heart Rhythm 2(6):624–631

    PubMed  Google Scholar 

  90. Kirchhof P, Klimas J, Fabritz L, Zwiener M, Jones LR, Schafers M et al (2007) Stress and high heart rate provoke ventricular tachycardia in mice expressing triadin. J Mol Cell Cardiol 42(5):962–971

    PubMed  CAS  Google Scholar 

  91. Schmitt FO, Erlanger J (1928) directional differences in the conduction of the impulse through heart muscle and their possible relation to extrasystolic and fibrillary contractions. Am J Physiol 87:326–341

    Google Scholar 

  92. Spach MS (1999) Anisotropy of cardiac tissue: a major determinant of conduction? J Cardiovasc Electrophysiol 10(6):887–890

    PubMed  CAS  Google Scholar 

  93. Allessie MA, Bonke FI, Schopman FJ (1976) Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes. Circ Res 39(2):168–177

    PubMed  CAS  Google Scholar 

  94. Allessie MA, Bonke FI, Schopman FJ (1977) Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The “leading circle” concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res 41(1):9–18

    PubMed  CAS  Google Scholar 

  95. el Sherif N (1988) Reentry revisited. Pacing Clin Electrophysiol 11(9):1358–1368

    PubMed  CAS  Google Scholar 

  96. Lin SF, Roth BJ, Wikswo JP Jr (1999) Quatrefoil reentry in myocardium: an optical imaging study of the induction mechanism. J Cardiovasc Electrophysiol 10(4):574–586

    PubMed  CAS  Google Scholar 

  97. Davidenko JM, Kent PF, Chialvo DR, Michaels DC, Jalife J (1990) Sustained vortex-like waves in normal isolated ventricular muscle. Proc Natl Acad Sci USA 87(22):8785–8789

    PubMed  CAS  Google Scholar 

  98. Pertsov AM, Davidenko JM, Salomonsz R, Baxter WT, Jalife J (1993) Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. Circ Res 72(3):631–650

    PubMed  CAS  Google Scholar 

  99. Anumonwo JM, Delmar M, Vinet A, Michaels DC, Jalife J (1991) Phase resetting and entrainment of pacemaker activity in single sinus nodal cells. Circ Res 68(4):1138–1153

    PubMed  CAS  Google Scholar 

  100. Athill CA, Ikeda T, Kim YH, Wu TJ, Fishbein MC, Karagueuzian HS et al (1998) Transmembrane potential properties at the core of functional reentrant wave fronts in isolated canine right atria. Circulation 98(15):1556–1567

    PubMed  CAS  Google Scholar 

  101. Vaidya D, Morley GE, Samie FH, Jalife J (1999) Reentry and fibrillation in the mouse heart. A challenge to the critical mass hypothesis. Circ Res 85(2):174–181

    PubMed  CAS  Google Scholar 

  102. Waldecker B, Coromilas J, Saltman AE, Dillon SM, Wit AL (1993) Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment. Circulation 87(4):1286–1305

    PubMed  CAS  Google Scholar 

  103. Davidenko JM (1993) Spiral wave activity: a possible common mechanism for polymorphic and monomorphic ventricular tachycardias. J Cardiovasc Electrophysiol 4(6):730–746

    PubMed  CAS  Google Scholar 

  104. Qu Z, Weiss JN, Garfinkel A (1999) Cardiac electrical restitution properties and stability of reentrant spiral waves: a simulation study. Am J Physiol 276(1 Pt 2):H269–H283

    PubMed  CAS  Google Scholar 

  105. Antzelevitch C, Jalife J, Moe GK (1980) Characteristics of reflection as a mechanism of reentrant arrhythmias and its relationship to parasystole. Circulation 61(1):182–191

    PubMed  CAS  Google Scholar 

  106. Antzelevitch C, Moe GK (1981) Electrotonically mediated delayed conduction and reentry in relation to “slow responses” in mammalian ventricular conducting tissue. Circ Res 49(5):1129–1139

    PubMed  CAS  Google Scholar 

  107. Antzelevitch C, Bernstein MJ, Feldman HN, Moe GK (1983) Parasystole, reentry, and tachycardia: a canine preparation of cardiac arrhythmias occurring across inexcitable segments of tissue. Circulation 68(5):1101–1115

    PubMed  CAS  Google Scholar 

  108. Delmar M, Michaels DC, Jalife J (1989) Slow recovery of excitability and the Wenckebach phenomenon in the single guinea pig ventricular myocyte. Circ Res 65(3):761–774

    PubMed  CAS  Google Scholar 

  109. Rosenthal JE (1988) Reflected reentry in depolarized foci with variable conduction impairment in 1 day old infarcted canine cardiac tissue. J Am Coll Cardiol 12(2):404–411

    PubMed  CAS  Google Scholar 

  110. Van Hemel NM, Swenne CA, de Bakker JM, Defauw JJ, Guiraudon GM (1988) Epicardial reflection as a cause of incessant ventricular bigeminy. Pacing Clin Electrophysiol 11(7):1036–1044

    PubMed  Google Scholar 

  111. Antzelevitch C, Yan GX (2010) J Wave Syndromes. Heart Rhythm 7(4):549–558

    Google Scholar 

  112. Antzelevitch C, Sicouri S, Litovsky SH, Lukas A, Krishnan SC, Di Diego JM et al (1991) Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ Res 69(6):1427–1449

    PubMed  CAS  Google Scholar 

  113. Antzelevitch C, Shimizu W, Yan GX, Sicouri S, Weissenburger J, Nesterenko VV et al (1999) The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 10(8):1124–1152

    PubMed  CAS  Google Scholar 

  114. Di Diego JM, Sun ZQ, Antzelevitch C (1996) I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium. Am J Physiol 271(2 Pt 2):H548–H561

    PubMed  Google Scholar 

  115. Volders PG, Sipido KR, Vos MA, Spatjens RL, Leunissen JD, Carmeliet E et al (1999) Downregulation of delayed rectifier K(+) currents in dogs with chronic complete atrioventricular block and acquired Torsades de Pointes. Circulation 100(24):2455–2461

    PubMed  CAS  Google Scholar 

  116. Zygmunt AC, Eddlestone GT, Thomas GP, Nesterenko VV, Antzelevitch C (2001) Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle. Am J Physiol Heart Circ Physiol 281(2):H689–H697

    PubMed  CAS  Google Scholar 

  117. Zygmunt AC, Goodrow RJ, Antzelevitch C (2000) I(NaCa) contributes to electrical heterogeneity within the canine ventricle. Am J Physiol Heart Circ Physiol 278(5):H1671–H1678

    PubMed  CAS  Google Scholar 

  118. Yan GX, Shimizu W, Antzelevitch C (1998) Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations. Circulation 98(18):1921–1927

    PubMed  CAS  Google Scholar 

  119. Sicouri S, Antzelevitch C (1993) Drug-induced afterdepolarizations and triggered activity occur in a discrete subpopulation of ventricular muscle cells (M cells) in the canine heart: quinidine and digitalis. J Cardiovasc Electrophysiol 4(1):48–58

    PubMed  CAS  Google Scholar 

  120. Sicouri S, Fish J, Antzelevitch C (1994) Distribution of M cells in the canine ventricle. J Cardiovasc Electrophysiol 5(10):824–837

    PubMed  CAS  Google Scholar 

  121. Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT et al (2008) T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 41(6):567–574

    PubMed  Google Scholar 

  122. Lubinski A, Lewicka-Nowak E, Kempa M, Baczynska AM, Romanowska I, Swiatecka G (1998) New insight into repolarization abnormalities in patients with congenital long QT syndrome: the increased transmural dispersion of repolarization. Pacing Clin Electrophysiol 21(1 Pt 2):172–175

    PubMed  CAS  Google Scholar 

  123. Wolk R, Mazurek T, Lusawa T, Wasek W, Rezler J (2001) Left ventricular hypertrophy increases transepicardial dispersion of repolarisation in hypertensive patients: a differential effect on QTpeak and QTend dispersion. Eur J Clin Invest 31(7):563–569

    PubMed  CAS  Google Scholar 

  124. Tanabe Y, Inagaki M, Kurita T, Nagaya N, Taguchi A, Suyama K et al (2001) Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome. J Am Coll Cardiol 37(3):911–919

    PubMed  CAS  Google Scholar 

  125. 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. Clin Sci (Lond) 105(6):671–676

    Google Scholar 

  126. Takenaka K, Ai T, Shimizu W, Kobori A, Ninomiya T, Otani H et al (2003) Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome. Circulation 107(6):838–844

    PubMed  Google Scholar 

  127. Wang D, Patel C, Cui C, Yan GX (2008) Preclinical assessment of drug-induced proarrhythmias: role of the arterially perfused rabbit left ventricular wedge preparation. Pharmacol Ther 119(2):141–151

    PubMed  CAS  Google Scholar 

  128. Pertsov AM, Jalife J (1995) Three-dimensional vortex-like reentry. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology: from cell to bedside. W.B. Saunders, Philadelphia, pp 403–410

    Google Scholar 

  129. Qu Z, Garfinkel A (2004) Nonlinear dynamics of excitation and propagation in cardiac muscle. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology: from cell to bedside. W.B. Saunders, Philadelphia, pp 327–335

    Google Scholar 

  130. Antzelevitch C (1983) Clinical application of new concepts of parasystole, reflection, and tachycardia. Cardiol Clin 1(1):39–50

    PubMed  CAS  Google Scholar 

  131. Antzelevitch C (1990) Electrotonus and reflection. In: Rosen MR, Janse MJ, Wit AL (eds) Cardiac electrophysiology: a textbook. Futura, Mount Kisco, NY, pp 491–516

    Google Scholar 

  132. Fish JM, Antzelevitch C (2004) Role of sodium and calcium channel block in unmasking the Brugada syndrome. Heart Rhythm 1(2):210–217

    PubMed  Google Scholar 

  133. Liu DW, Gintant GA, Antzelevitch C (1993) Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 72(3):671–687

    PubMed  CAS  Google Scholar 

  134. Yan GX, Antzelevitch C (1998) Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 98(18):1928–1936

    PubMed  CAS  Google Scholar 

  135. Antzelevitch C (2006) Brugada syndrome. Pacing Clin Electrophysiol 29(10):1130–1159

    PubMed  Google Scholar 

  136. Patel C, Antzelevitch C (2008) Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm 5(4):585–590

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Masonic Medical Research Laboratory, Utica, NY, USA

    Charles Antzelevitch PhD

  2. Main Line Health Heart Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA

    Gan-Xin Yan MD, PhD

  3. Division of Cardiovascular Diseases, Jefferson Medical College, Philadelphia, PA, USA

    Gan-Xin Yan MD, PhD

  4. Xi’an Jiaotong University, Xi’an, China

    Gan-Xin Yan MD, PhD

Authors
  1. Charles Antzelevitch PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gan-Xin Yan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Main Line Health Heart Center, 100 Lancaster Ave, Wynnewood, 19096, Pennsylvania, USA

    Gan-Xin Yan

  2. Main Line Health Heart Center, 100 Lancaster Ave, Wynnewood, 19096, Pennsylvania, USA

    Peter R. Kowey

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Antzelevitch, C., Yan, GX. (2011). Ionic and Cellular Basis for Arrhythmogenesis. In: Yan, GX., Kowey, P. (eds) Management of Cardiac Arrhythmias. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-161-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-161-5_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-160-8

  • Online ISBN: 978-1-60761-161-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation