Advertisement

The Virtual Electrode Hypothesis of Defibrillation

  • Crystal M. Ripplinger
  • Igor R. Efimov

Despite significant research efforts of investigators in academia, medicine, and the pharmaceutical industry, no effective pharmacological alternative to defibrillation by electric shock has been developed. Thus, defibrillation has evolved to become the only effective therapy against sudden cardiac death. Highly detailed knowledge of ion channel biophysics and cell signaling cascades has allowed for the development of numerous specific agonists and antagonists, but as of yet, has failed to deliver safe and effective antiarrhythmic therapy. In contrast to this approach, electrotherapy is steadily improving its efficacy and safety.

Despite major improvements over the past several decades, defibrillation is not free from side effects, which may include both contractile and electrical dysfunction.1–3 In addition to physical damage to the heart, defibrillation is also associated with psychological side effects.4,5 Therefore, reduction of defibrillation energy is highly desirable. However, the basic mechanisms of defibrillation still remain debatable a century after its inception, which has slowed further improvement of the therapy. This chapter explores one of the leading hypotheses of defibrillation, the virtual electrode hypothesis, which has emerged over the past decade through the successes of novel research methodologies, including optical mapping and bidomain modeling.

Keywords

Right Ventricle Negative Polarization Transmembrane Potential Spiral Wave Optical Mapping 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Al Khadra A, Nikolski V, Efimov IR. The role of electroporation in defibrillation. Circ Res 2000;87(9):797–804Google Scholar
  2. 2.
    Kodama I, Shibata N, Sakuma I, Mitsui K, Iida M, Suzuki R, Fukui Y, Hosoda S, Toyama J. Aftereffects of high-intensity DC stimulation on the electromechanical performance of ventricular muscle. Am J Physiol 267(1 Pt 2):H248–H258Google Scholar
  3. 3.
    Neunlist M, Tung L. Dose-dependent reduction of cardiac transmembrane potential by high-intensity electrical shocks. Am J Physiol 273(6 Pt 2):H2817–H2825Google Scholar
  4. 4.
    Godemann F, Butter C, Lampe F, Linden M, Schlegl M, Schultheiss HP, Behrens S. Panic disorders and agoraphobia: side effects of treatment with an implantable cardioverter/defibrillator. Clin Cardiol 27(6):321–326Google Scholar
  5. 5.
    Kamphuis HC, de Leeuw JR, Derksen R, Hauer RN, Winnubst JA. Implantablecardioverter defibrillator recipients: quality of life in recipients with and without ICD shock delivery: a prospective study. Europace 5(4):381–389Google Scholar
  6. 6.
    Fye WB. Ventricular fibrillation and defibrillation: historical perspectives with emphasis on the contributions of John MacWilliam, Carl Wiggers, and William Kouwenhoven.Circ 1985;71(5):858–865Google Scholar
  7. 7.
    Prevost JL, Battelli F. Sur quel ques effets des dechanges electriques sur le coer mammifres. C R Seances Acad Sci 1899;129:1267Google Scholar
  8. 8.
    Gurvich NL, Yuniev GS. Restoration of regular rhythm in the mammalian fibrillating heart. Am Rev Sov Med 1946;3:236–239Google Scholar
  9. 9.
    Beck CS, Pritchard WH, Feil HS. Ventricular fibrillation of long duration abolished by electric shock. JAMA 1947;135:985Google Scholar
  10. 10.
    Zoll PM, Linethal AJ, Gibson W, et al. Termination of ventricular fibrillation in man by externally applied electric shock. N Engl J Med 1956;254:727PubMedGoogle Scholar
  11. 11.
    Kouwenhoven WB, Milnor WR. Treatment of ventricular fibrillation using a capacitor discharge. J Appl Physiol 1954;7(3):253–257PubMedGoogle Scholar
  12. 12.
    Lown B, Neuman J, Amarasingham R, Berkovits BV. Comparison of alternating current with direct electroshock across the closed chest. Am J Cardiol 1962;10:223–233PubMedCrossRefGoogle Scholar
  13. 13.
    Gurvich NL. The Main Principles of Cardiac Defibrillation. Moscow: Medicine; 1975Google Scholar
  14. 14.
    Mirowski M, Mower MM, Reid PR. The automatic implantable defibrillator. Am Heart J 1980;100(6 Pt 2):1089–1092PubMedCrossRefGoogle Scholar
  15. 15.
    Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF, Langer A, Heil-man MS, Kolenik SA, Fischell RE, Weisfeldt ML. Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med1980;303(6):322–324PubMedGoogle Scholar
  16. 16.
    Tung L. A Bidomain Model for Describing Ischemia Myocardial DC Potentials. Cambridge, MA: Massachusetts Institute of Technology; 1978Google Scholar
  17. 17.
    Henriquez CS. Simulating the electrical behavior of cardiac tissue using the bidomain model. Crit Rev Biomed Eng 1993;21(1):1–77PubMedGoogle Scholar
  18. 18.
    Skouibine K, Trayanova N, Moore P. A numerically efficient model for simulation of defibrillation in an active bidomain sheet of myocardium. Math Biosci 2000;166(1):85–100PubMedCrossRefGoogle Scholar
  19. 19.
    Krassowska W. Effects of electroporation on transmembrane potential induced by defibrillation shocks. Pacing Clin Electrophysiol 1995;18(9 Pt 1):1644–1660PubMedCrossRefGoogle Scholar
  20. 20.
    Beeler GW, Reuter H. Reconstruction of the action potential of ventricular myocardial fibres. J Physiol (Lond) 1977;268(1):177–210Google Scholar
  21. 21.
    Drouhard JP, Roberge FA. A simulation study of the ventricular myocardial action potential. IEEE Trans Biomed Eng 1982;29(7):494–502PubMedCrossRefGoogle Scholar
  22. 22.
    Luo CH, Rudy Y. A model of the ventricular cardiac action potential. Depolarization,repolarization, and their interaction. Circ Res 1991;68(6):1501–1526PubMedGoogle Scholar
  23. 23.
    Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential. I.Simulations of ionic currents and concentration changes. Circ Res 1994;74(6):1071–1096PubMedGoogle Scholar
  24. 24.
    Hund TJ, Rudy Y. Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model. Circulation 2004;110(20):3168–3174Google Scholar
  25. 25.
    Hodgkin AL, Huxley AF. Propagation of electrical signals along giant nerve fibers. Proc R Soc Lond B Biol Sci 1952;140(899):177–183PubMedGoogle Scholar
  26. 26.
    Cohen LB, Lesher S, De Weer P, Salzberg BM. Optical monitoring of membrane potential: methods of multisite optical measurement. Optical Methods in Cell Physiology. New York: Wiley-Interscience; 1986:71–100Google Scholar
  27. 27.
    Davila HV, Salzberg BM, Cohen LB, Waggoner AS. A large change in axon fluorescence that provides a promising method for measuring membrane potential. Nat New Biol 1973;241(109):159–160PubMedGoogle Scholar
  28. 28.
    Salama G, Morad M. Merocyanine 540 as an optical probe of transmembrane electrical activity in the heart. Science 1976;191(4226):485–487PubMedCrossRefGoogle Scholar
  29. 29.
    Morad M, Salama G. Optical probes of membrane potential in heart muscle. J Physiol (Lond) 1979;292:267–295Google Scholar
  30. 30.
    Ross WN, Salzberg BM, Cohen LB, Grinvald A, Davila HV, Waggoner AS, Wang CH.Changes in absorption, fluorescence, dichroism, and birefringence in stained giant axons:optical measurement of membrane potential. J Membr Biol 1977;33(1–2):141–183PubMedGoogle Scholar
  31. 31.
    Salama G, Loew LM. Optical measurements of transmembrane potential in heart.Spectroscopic Membrane Probes. Boca Raton, FL: CRC; 1988:137–199Google Scholar
  32. 32.
    Dillon S, Morad M. A new laser scanning system for measuring action potential propagation in the heart. Science 1981;214(4519):453–456PubMedCrossRefGoogle Scholar
  33. 33.
    Kodama I, Sakuma I, Shibata N, Knisley SB, Niwa R, Honjo H. Regional differences in arrhythmogenic aftereffects of high intensity DC stimulation in the ventricles. Pacing Clin Electrophysiol 2000;23(5):807–817PubMedCrossRefGoogle Scholar
  34. 34.
    Entcheva E, Kostov Y, Tchernev E, Tung L. Fluorescence imaging of electrical activity in cardiac cells using an all-solid-state system. IEEE Trans Biomed Eng2004;51(2):333–341PubMedCrossRefGoogle Scholar
  35. 35.
    Amino M, Yamazaki M, Nakagawa H, Honjo H, Okuno Y, Yoshioka K, Tanabe T,Yasui K, Lee JK, Horiba M, Kamiya K, Kodama I. Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium. Circ J 2005;69(5):576–584PubMedCrossRefGoogle Scholar
  36. 36.
    Bray MA, Lin SF, Wikswo JP. Panoramic epifluorescent visualization of cardiac action potential activity. Proc SPIE 1999;3658:99–107CrossRefGoogle Scholar
  37. 37.
    Lin SF, Wikswo JP. Panoramic optical imaging of electrical propagation in isolated heart. J Biomed Opt 1999;4(2):200–207CrossRefGoogle Scholar
  38. 38.
    Bray MA, Lin SF, Wikswo J. Three-dimensional visualization of phase singularities on the isolated rabbit heart. J Cardiovasc Electrophysiol 2002;13(12):1311Google Scholar
  39. 39.
    Kay MW, Amison PM, Rogers JM. Three-dimensional surface reconstruction and panoramic optical mapping of large hearts. IEEE Trans Biomed Eng 2004;51(7):1219–1229PubMedCrossRefGoogle Scholar
  40. 40.
    Qu F, Ripplinger CM, Nikolski VP, Grimm C, Efimov IR. Three dimensional panoramic imaging of cardiac arrhythmias in the rabbit heart. J Biomed Opt 2007;12(4):044019PubMedCrossRefGoogle Scholar
  41. 41.
    Furman S, Hurzeler P, Parker B. Clinical thresholds of endocardial cardiac stimulation:a long-term study. J Surg Res 1975;19:149–155PubMedCrossRefGoogle Scholar
  42. 42.
    Rattay F. Analysis of models for extracellular fiber stimulation. IEEE Trans Biomed Eng 1989;36(7):676–682PubMedCrossRefGoogle Scholar
  43. 43.
    Sobie EA, Susil RC, Tung L. A generalized activating function for predicting virtualelectrodes in cardiac tissue. Biophysical J 1997;73(3):1410–1423CrossRefGoogle Scholar
  44. 44.
    Sepulveda NG, Roth BJ, Wikswo JP. Current injection into a two-dimensional anisotropic bidomain.Biophysical J1989;55(5):987–999Google Scholar
  45. 45.
    Wikswo JP, Lin SF, Abbas RA. Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation.Biophysical J1995;69(6):2195–2210Google Scholar
  46. 46.
    Fast VG, Rohr S, Gillis AM, Kleber AG. Activation of cardiac tissue by extracellular electrical shocks: formation of ‘secondary sources’ at intercellular clefts in monolayers of cultured myocytes.Circ Res1998;82(3):375–385PubMedGoogle Scholar
  47. 47.
    Trayanova N, Skouibine K, Aguel F. The role of cardiac tissue structure in defibrillation.Chaos1998;8(1):221–233PubMedCrossRefGoogle Scholar
  48. 48.
    Gurvich NL, Yuniev GS. Restoration of regular rhythm in the mammalian fibrillating heart.Byull Eksper Biol Med1939;8(1):55–58Google Scholar
  49. 49.
    Zipes DP, Fischer J, King RM, Nicoll Ad, Jolly WW. Termination of ventricular fibrillation in dogs by depolarizing a critical amount of myocardium.Am J Cardiol1975;36(1):37–44PubMedCrossRefGoogle Scholar
  50. 50.
    Witkowski FX, Penkoske PA, Plonsey R. Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled simultaneous activation and shock potential recordings.Circulation1990;82(1):244–260PubMedGoogle Scholar
  51. 51.
    Krinskii VI, Fomin SV, Kholopov AV. [Critical mass during fibrillation].Biofizika1967;12(5):908–914PubMedGoogle Scholar
  52. 52.
    Fabiato A, Coumel P, Gourgon R, Saumont R. The threshold of synchronous response of the myocardial fibers. Application to the experimental comparison of the efficacy of different forms of electroshock defibrillation.Arch Mal Coeur Vaiss1967;60(4):527–544PubMedGoogle Scholar
  53. 53.
    Chen PS, Shibata N, Dixon EG, Martin RO, Ideker RE. Comparison of the defibrillation threshold and the upper limit of ventricular vulnerability.Circulation1986;73(5):1022–1028PubMedGoogle Scholar
  54. 54.
    Shibata N, Chen PS, Dixon EG, Wolf PD, Danieley ND, Smith WM, Ideker RE.Influence of shock strength and timing on induction of ventricular arrhythmias in dogs.Am J Physiol1988;255(4 Pt 2):H891–H901PubMedGoogle Scholar
  55. 55.
    Fabritz CL, Kirchhof PF, Behrens S, Zabel M, Franz MR. Myocardial vulnerability to T wave shocks: relation to shock strength, shock coupling interval, and dispersion of ventricular repolarization.J Cardiovasc Electrophysiol1996;7(3):231–242PubMedCrossRefGoogle Scholar
  56. 56.
    Chen PS, Feld GK, Kriett JM, Mower MM, Tarazi RY, Fleck RP, Swerdlow CD, Gang ES, Kass RM. Relation between upper limit of vulnerability and defibrillation threshold in humans.Circulation1993;88(1):186–192PubMedGoogle Scholar
  57. 57.
    Hwang C, Swerdlow CD, Kass RM, Gang ES, Mandel WJ, Peter CT, Chen PS. Upper limit of vulnerability reliably predicts the defibrillation threshold in humans.Circulation1994;90(5):2308–2314PubMedGoogle Scholar
  58. 58.
    Wiener N, Rosenblueth A. The mathematical formulation of the problem of conduction of impulses in a network of connected excitable elements, specifically in cardiac muscle.Arch Inst Cardiol Mexico1946;16(3–4):205–265PubMedGoogle Scholar
  59. 59.
    Frazier DW, Wolf PD, Wharton JM, Tang AS, Smith WM, Ideker RE. Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.J Clin Invest1989;83(3):1039–1052PubMedCrossRefGoogle Scholar
  60. 60.
    Walcott GP, Walcott KT, Knisley SB, Zhou X, Ideker RE. Mechanisms of defibrillation for monophasic and biphasic waveforms.Pacing Clin Electrophysiol1994;17(3 Pt 2):478–498PubMedCrossRefGoogle Scholar
  61. 61.
    Walcott GP, Walcott KT, Ideker RE. Mechanisms of defibrillation. Critical points and the upper limit of vulnerability.J Electrocardiol1995;28(Suppl):1–6PubMedCrossRefGoogle Scholar
  62. 62.
    Dillon SM, Kwaku KF. Progressive depolarization: a unified hypothesis for defibrillation and fibrillation induction by shocks.J Cardiovasc Electrophysiol1998;9(5):529–552PubMedCrossRefGoogle Scholar
  63. 63.
    Roth BJ. A mathematical model of make and break electrical stimulation of cardiac tissue by a unipolar anode or cathode.IEEE Trans Biomed Eng1995;42(12):1174–1184PubMedCrossRefGoogle Scholar
  64. 64.
    Knisley SB, Hill BC, Ideker RE. Virtual electrode effects in myocardial fibers.Biophysical J1994;66(3 Pt 1):719–728Google Scholar
  65. 65.
    Neunlist M, Tung L. Spatial distribution of cardiac transmembrane potentials around an extracellular electrode: dependence on fiber orientation.Biophysical J1995;68(6):2310–2322Google Scholar
  66. 66.
    Efimov IR, Cheng YN, Biermann M, Van Wagoner DR, Mazgalev T, Tchou PJ. Trans-membrane voltage changes produced by real and virtual electrodes during monophasic defibrillation shock delivered by an implantable electrode.J Cardiovasc Electrophysiol1997;8:1031–1045PubMedCrossRefGoogle Scholar
  67. 67.
    Efimov IR, Cheng Y, Van Wagoner DR, Mazgalev T, Tchou PJ. Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure.Circ Res1998;82(8):918–925PubMedGoogle Scholar
  68. 68.
    Efimov IR, Gray RA, Roth BJ. Virtual electrodes and de-excitation: new insights into fibrillation induction and defibrillation.J Cardiovasc Electrophysiol2000;11(3):339–353PubMedCrossRefGoogle Scholar
  69. 69.
    Cheng Y, Mowrey KA, Van Wagoner DR, Tchou PJ, Efimov IR. Virtual electrode induced re-excitation: a basic mechanism of defibrillation.Circ Res1999;85(11):1056–1066PubMedGoogle Scholar
  70. 70.
    Hoffa M, Ludwig C. Einige neue Versuche uber Herzbewegung.Zeitschrift Rationelle Medizin1850;9:107–144Google Scholar
  71. 71.
    Skouibine K, Trayanova NA, Moore P. Anode/cathode make and break phenomena in a model of defibrillation.IEEE Trans Biomed Eng1999;46(7):769–777PubMedCrossRefGoogle Scholar
  72. 72.
    Lin SF, Roth BJ, Wikswo JP. Quatrefoil reentry in myocardium: an optical imaging study of the induction mechanism.J Cardiovasc Electrophysiol1999;10:574–586PubMedCrossRefGoogle Scholar
  73. 73.
    Winfree AT.When Time Breaks Down: The Three-Dimensional Dynamics of Electrochemical Waves and Cardiac Arrhythmias. Princeton, NJ: Princeton University Press;1987Google Scholar
  74. 74.
    Cheng Y, Van Wagoner D, Tchou PJ, Efimov IR. Defibrillation shock-induced waves of re-excitation: implications to upper and lower limits of vulnerability.PAC E1999;22(4(II)):809Google Scholar
  75. 75.
    Cheng Y, Nikolski V, Efimov IR. Reversal of repolarization gradient does not reverse the chirality of shock-induced reentry in the rabbit heart.J Cardiovasc Electrophysiol2000;11(9):998–1007PubMedCrossRefGoogle Scholar
  76. 76.
    Efimov IR, Cheng Y, Yamanouchi Y, Tchou PJ. Direct evidence of the role of virtual electrode induced phase singularity in success and failure of defibrillation.J Cardiovasc Electrophysiol2000;11(8):861–868PubMedCrossRefGoogle Scholar
  77. 77.
    Jones JL, Jones RE, Balasky G. Microlesion formation in myocardial cells by high-intensity electric field stimulation.Am J Physiol1987;253(2 Pt 2):H480–H486PubMedGoogle Scholar
  78. 78.
    Nikolski VP, Sambelashvili AT, Krinsky VI, Efimov IR. Effects of electroporation on optically recorded transmembrane potential responses to high-intensity electrical shocks.Am J Physiol Heart Circ Physiol2004;286(1):H412–H418PubMedCrossRefGoogle Scholar
  79. 79.
    Yamanouchi Y, Cheng Y, Tchou PJ, Efimov IR. The mechanisms of vulnerable window: the role of virtual electrodes and shock polarity.Can J Physiol Pharmacol2001;79(1):25–33PubMedCrossRefGoogle Scholar
  80. 80.
    Kroll MW, Efimov IR, Tchou PJ. Present understanding of shock polarity for internal defibrillation: the obvious and non-obvious clinical implications.Pacing Clin Electro-physiol2006;29(8):885–891CrossRefGoogle Scholar
  81. 81.
    Chapman PD, Vetter JW, Souza JJ, Troup PJ, Wetherbee JN, Hoffmann RG. Comparative efficacy of monophasic and biphasic truncated exponential shocks for nontho-racotomy internal defibrillation in dogs.J Am Coll Cardiol1988;12(3):739–745PubMedCrossRefGoogle Scholar
  82. 82.
    Feeser SA, Tang AS, Kavanagh KM, Rollins DL, Smith WM, Wolf PD, Ideker RE.Strength-duration and probability of success curves for defibrillation with biphasic waveforms.Circulation1990;82(6):2128–2141PubMedGoogle Scholar
  83. 83.
    Qu F, Li L, Nikolski VP, Sharma V, Efimov IR. Mechanisms of superiority of ascending ramp waveforms: new insights into mechanisms of shock-induced vulnerability and defibrillation.Am J Physiol Heart Circ Physiol2005;289(2):H569–H577PubMedCrossRefGoogle Scholar
  84. 84.
    Takagi S, Pumir A, Pazo D, Efimov I, Nikolski V, Krinsky V. Unpinning and removal of a rotating wave in cardiac muscle.Phys Rev Lett2004;93(5):058101PubMedCrossRefGoogle Scholar
  85. 85.
    Ripplinger CM, Krinsky VI, Nikolski VP, Efimov IR. Mechanisms of unpinning and termination of ventricular tachycardia.Am J Physiol Heart Circ Physiol2006;291(1):H184–H192PubMedCrossRefGoogle Scholar
  86. 86.
    Fedorov VV, Schuessler RB, Lall S, Ripplinger CM, Sakamoto S, Efimov IR. Low voltage defibrillation of sustained ventricular tachycardia in infarcted canine hearts.Heart Rhythm2007;4 (5S):S171Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Crystal M. Ripplinger
    • 1
  • Igor R. Efimov
    1. 1.Department of Biomedical EngineeringInstitute for Computational Medicine, Johns Hopkins UniversityUSA

    Personalised recommendations