Advertisement

The Role of Microscopic Tissue Structure in Defibrillation

  • Vladimir G. Fast

Ventricular fibrillation is the most important immediate cause of sudden cardiac death, which is the main source of mortality in developed countries. Currently, the only practical method for treating ventricular fibrillation is electrical defibrillation. External defibrillators accessible to public and implantable devices are becoming more widespread, reducing the risk of sudden cardiac death. Nevertheless, current defibrillation techniques have significant drawbacks. Shocks can be detrimental by causing pain, tissue damage, and reinducing arrhythmias.1 In addition, shocks may fail, which requires multiple shock application,2 or fibrillation can be terminated but normal heartbeat and blood circulation not restored.3,4 Therefore, there is a need to increase defibrillation efficacy and reduce its side effects, which underlies the continuing search for better defibrillation techniques. This search would have higher chances for success if it were guided by the exact knowledge of the defibrillation mechanism. Significant advances in understanding defibrillation were made in recent years using sophisticated electrical and optical mapping techniques as well as advanced mathematical models of cardiac excitation that provided a wealth of new information about the effects of electrical fields on cardiac tissue. Despite these efforts the defibrillation mechanism still remains a mystery. One of the main unresolved questions is why an electrical shock causes any significant effect on the heart at all; the other question is how exactly the shock affects the heart and stops abnormal electrical activity. Fibrillation is generally considered a distributed process, which is maintained by multiple reentrant circuits or randomly wandering wavelets in various parts of the heart.5–7 To interrupt such fibrillation, all reentrant wavefronts have to be extinguished. According to the “excitatory” hypothesis of defibrillation, this is achieved by simultaneous activation of cardiac tissue in the excitable and relatively refractory states.8,9 The newly depolarized tissue presents functional obstacles to excitation waves, blocking their propagation and, therefore, arresting fibrillation. An important requirement of defibrillation is that abnormal activity must be stopped in a critical mass of ventricular myocardium estimated at 80–90% of the total mass.9,10 This means that the shock must change membrane potential (V m) of nearly all cardiac cells across the ventricular wall. How this global shock effect is achieved is not presently known. The classical cable model of cardiac muscle indicates that shock-induced V m changes should be restricted only to the tissue near shock electrodes or muscle surface,11 leaving the intramural bulk of the myocardium unaffected by the shock. This model's prediction about the locality of shock effects is in stark contradiction with the distributed nature of fibrillation. This contradiction was recognized about 20 years ago.12–14 To resolve it, a so-called secondary source hypothesis was proposed, which linked shock effects with the microscopic tissue structure. More specifically, it was postulated that shocks cause widespread changes of V m due to numerous microscopic discontinuities in the tissue structure, such as cell boundaries.12–14

Keywords

Secondary Source Action Potential Duration Optical Mapping Shock Strength Action Potential Amplitude 
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.
    Tung L. Detrimental effects of electrical fields on cardiac muscle. Proc IEEE 1996;84:366–378CrossRefGoogle Scholar
  2. 2.
    Valenzuela TD, Roe DJ, Cretin S, Spaite DW, Larsen MP. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation 1997;96:3308–3313PubMedGoogle Scholar
  3. 3.
    Garcia LA, Allan JJ, Kerber RE. Interactions between CPR and defibrillation waveforms: effect on resumption of a perfusing rhythm after defibrillation. Resuscitation 2000;47:301–305PubMedCrossRefGoogle Scholar
  4. 4.
    Geddes LA, Roeder RA, Kemeny A, Otlewski M. The duration of ventricular fibrillation required to produce pulseless electrical activity. Am J Emerg Med 2005;23: 138–141PubMedCrossRefGoogle Scholar
  5. 5.
    Kléber AG, Janse MJ, Fast VG. Normal and abnormal conduction in the heart. Handbook of Physiology. Section 2: The Cardiovascular System. Oxford: Oxford University Press; 2001:455–530Google Scholar
  6. 6.
    Chen PS, Wu TJ, Ting CT, Karagueuzian HS, Garfinkel A, Lin SF, Weiss JN. A tale of two fibrillations. Circulation 2003;108:2298–2303PubMedCrossRefGoogle Scholar
  7. 7.
    Weiss JN, Chen PS, Wu TJ, Siegerman C, Garfinkel A. Ventricular fibrillation: new insights into mechanisms. Ann N Y Acad Sci 2004;1015:122–132PubMedCrossRefGoogle Scholar
  8. 8.
    Gurvich NL, Yuneiv GS. Restoration of regular rhythm in the mammalian fibrillating heart. Am Rev Sov Med 1946;3:236–239Google Scholar
  9. 9.
    Zipes DP, Fisher J, King RM, Nicoll AB, Jolly WW. Termination of ventricular fibrillation in dogs by depolarizing a critical amount of myocardium. Am J Cardiol 1975;36:37–44PubMedCrossRefGoogle Scholar
  10. 10.
    Zhou XH, Daubert JP, Wolf PD, Smith WM, Ideker RE. Epicardial mapping of ventricular defibrillation with monophasic and biphasic shocks in dogs. Circ Res 1993;72:145– 160PubMedGoogle Scholar
  11. 11.
    Weidmann S. Electrical constants of trabecular muscle from mammalian heart. J Physiol 1970;210:1041–1054PubMedGoogle Scholar
  12. 12.
    Plonsey R, Barr RC. Effect of microscopic and macroscopic discontinuities on the response of cardiac tissue to defibrillating (stimulating) currents. Med Biol Eng Comput 1986;24:130–136PubMedCrossRefGoogle Scholar
  13. 13.
    Plonsey R, Barr RC. Inclusion of junction elements in a linear cardiac model through secondary sources: application to defibrillation. Med Biol Eng Comput 1986;24: 137–144PubMedCrossRefGoogle Scholar
  14. 14.
    Krassowska W, Pilkington T, Ideker RE. Periodic conductivity as a mechanism for cardiac stimulation and defibrillation. IEEE Trans Biomed Eng 1987;34:555–560PubMedCrossRefGoogle Scholar
  15. 15.
    Trayanova N, Plank G, Rodriguez B. What have we learned from mathematical models of defibrillation and postshock arrhythmogenesis? Application of bidomain simulations. Heart Rhythm 2006;3:1232–1235PubMedCrossRefGoogle Scholar
  16. 16.
    Fishler MG. Syncytial heterogeneity as a mechanism underlying cardiac far-field stimulation during defibrillation-level shocks. J Cardiovasc Electrophysiol 1998;9:384–394PubMedCrossRefGoogle Scholar
  17. 17.
    Rattay F. Analysis of models for extracellular fiber stimulation. IEEE Trans Biomed Eng 1989;36:676–682PubMedCrossRefGoogle Scholar
  18. 18.
    Wikswo JP, Lin S-F, Abbas RA. Virtual electrode effect in cardiac tissue: a common mechanism for anodal and cathodal stimulation. Biophys J 1995;69:2195–2210PubMedGoogle Scholar
  19. 19.
    Sobie E, Susil R, Tung L. A generalized activating function for predicting virtual electrodes in cardiac tissue. Biophys J 1997;73:1410–1423PubMedGoogle Scholar
  20. 20.
    Sepulveda NG, Roth BJ, Wikswo JP. Current injection into a two-dimensional anisotropic bidomain. Biophys J 1989;55:987–999PubMedCrossRefGoogle Scholar
  21. 21.
    Hooks DA, Tomlinson KA, Marsden SG, LeGrice IJ, Smaill BH, Pullan AJ, Hunter PJ. Cardiac microstructure: implications for electrical propagation and defibrillation in the heart. Circ Res 2002;91:331–338PubMedCrossRefGoogle Scholar
  22. 22.
    Fast VG, Kléber AG. Microscopic conduction in cultured strands of neonatal rat heart cells measured with voltage-sensitive dyes. Circ Res 1993;73:914–925PubMedGoogle Scholar
  23. 23.
    Gillis AM, Fast VG, Rohr S, Kléber AG. Effects of defibrillation shocks on the spatial distribution of the transmembrane potential in strands and monolayers of cultured neonatal rat ventricular myocytes. Circ Res 1996;79:676–690PubMedGoogle Scholar
  24. 24.
    Jongsma HJ, van Rijn HE. Electrotonic spread of current in monolayer cultures of neonatal rat heart cells. J Membr Biol 1972;9:341–360PubMedCrossRefGoogle Scholar
  25. 25.
    Sharma V, Tung L. Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs. J Cardiovasc Electrophysiol 2001;12:1164–1173PubMedCrossRefGoogle Scholar
  26. 26.
    Darrow BJ, Laing JG, Lampe PD, Saffitz JE, Beyer EC. Expression of multiple connexins in cultured neonatal rat ventricular myocytes. Circ Res 1995;76:381–387PubMedGoogle Scholar
  27. 27.
    Hoyt RH, Cihen ML, Saffitz JE. Distribution and three-dimensional structure of intercellular junctions in canine myocardium. Circ Res 1989;64:563–574PubMedGoogle Scholar
  28. 28.
    Luke RA, Beyer EC, Hoyt RH, Saffitz JE. Quantitative analysis of intercellular connections by immunohistochemistry of the cardiac gap junction protein Connexin43. Circ Res 1989;95:1450–1457Google Scholar
  29. 29.
    Zhou X, Knisley SB, Smith WM, Rollins D, Pollard AE, Ideker RE. Spatial changes in the transmembrane potential during extracellular electric stimulation. Circ Res 1998;83:1003–1014PubMedGoogle Scholar
  30. 30.
    Windisch H, Platzer D, Bilgici E. Quantification of shock-induced microscopic virtual electrodes assessed by subcellular resolution optical potential mapping in guinea pig papillary muscle. J Cardiovasc Electrophysiol 2007;18:1086–1094PubMedCrossRefGoogle Scholar
  31. 31.
    Fast VG, Rohr S, Gillis AM, Kléber AG. Activation of cardiac tissue by extracellular electrical shocks: formation of “secondary sources” at intercellular clefts in monolayers of cultured myocytes. Circ Res 1998;82:375–385PubMedGoogle Scholar
  32. 32.
    Spach MS, Dolber PC. Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res 1986;58:356–371PubMedGoogle Scholar
  33. 33.
    Le Grice IJ, Smaill BH, Chai LZ, Edgar SG, Gavin JB, Hunter PJ. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog. Am J Physiol 1995;38:H571–H582Google Scholar
  34. 34.
    Fast VG, Rohr S, Ideker RE. Non-linear changes of transmembrane potential caused by defibrillation shocks in strands of cultured myocytes. Am J Physiol 2000;278:H688–H697Google Scholar
  35. 35.
    Cheek ER, Ideker RE, Fast VG. Nonlinear changes of transmembrane potential during defibrillation shocks: role of Ca2+ current. Circ Res 2000;87:453–459PubMedGoogle Scholar
  36. 36.
    Fast VG, Cheek ER. Optical mapping of arrhythmias induced by strong electrical shocks in myocyte cultures. Circ Res 2002;90:664–670PubMedCrossRefGoogle Scholar
  37. 37.
    Zhou XH, Rollins DL, Smith WM, Ideker RE. Responses of the transmembrane potential of myocardial cells during a shock. J Cardiovasc Electrophysiol 1995;6: 252–263PubMedCrossRefGoogle Scholar
  38. 38.
    Zhou XH, Smith WM, Rollins DL, Ideker RE. Transmembrane potential changes caused by shocks in guinea pig papillary muscle. Am J Physiol 1996;271:H2536–H2546PubMedGoogle Scholar
  39. 39.
    Fast VG, Sharifov OF, Cheek ER, Newton J, Ideker RE. Intramural virtual electrodes during defibrillation shocks in left ventricular wall assessed by optical mapping of membrane potential. Circulation 2002;106:1007–1014PubMedCrossRefGoogle Scholar
  40. 40.
    Sharifov OF, Fast VG. Optical mapping of transmural activation induced by electrical shocks in isolated left ventricular wall wedge preparations. J Cardiovasc Electrophysiol 2003;14:1215–1222PubMedCrossRefGoogle Scholar
  41. 41.
    Efimov IR, Cheng Y, Van Wagoner DR, Mazgalev T, Tchou PJ. Virtual electrode-induced phase singularity. A basic mechanism of defibrillation failure. Circ Res 1998;82:918–925PubMedGoogle Scholar
  42. 42.
    Efimov IR, Gray RA, Roth BJ. Virtual electrodes and deexcitation: new insights into fibrillation induction and defibrillation. J Cardiovasc Electrophysiol 2000;11:339–353PubMedCrossRefGoogle Scholar
  43. 43.
    Cheek ER, Fast VG. Nonlinear changes of transmembrane potential during electrical shocks: role of membrane electroporation. Circ Res 2004;94:208–214PubMedCrossRefGoogle Scholar
  44. 44.
    Fast VG, Cheek ER, Pollard AE, Ideker RE. Effects of electrical shocks on Ca2 i + and V m in myocyte cultures. Circ Res 2004;94:1589–1597PubMedCrossRefGoogle Scholar
  45. 45.
    Raman V, Pollard AE, Fast VG. Shock-induced changes of Ca2 i + and V m in myocyte cultures and computer model: dependence on the timing of shock application. Cardiovasc Res 2006;73:101–110PubMedCrossRefGoogle Scholar
  46. 46.
    Sharma V, Tung L. Ionic currents involved in shock-induced nonlinear changes in transmembrane potential responses of single cardiac cells. Pflugers Arch 2004;449:248– 256PubMedGoogle Scholar
  47. 47.
    Yuan W, Ginsburg KS, Bers DM. Comparison of sarcolemmal calcium channel current in rabbit and rat ventricular myocytes. J Physiol 1996;493:733–746PubMedGoogle Scholar
  48. 48.
    Gomez JP, Potreau D, Branka JE, Raymond G. Developmental changes in Ca2+ currents from newborn rat cardiomyocytes in primary culture. Pflugers Arch 1994;428:241–249PubMedCrossRefGoogle Scholar
  49. 49.
    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 2004;286:H412–H418Google Scholar
  50. 50.
    Jones JL, Jones RE. Postshock arrhythmias—a possible cause of unsuccessful defibril-lation. Crit Care Med 1980;8:167–171PubMedCrossRefGoogle Scholar
  51. 51.
    Wharton JM, Wolf PD, Smith WM, Chen PS, Frazier DW, Yabe S, Danieley N, Ideker RE. Cardiac potential and potential gradient fields generated by single, combined, and sequential shocks during ventricular defibrillation. Circulation 1992;85:1510–1523PubMedGoogle Scholar
  52. 52.
    Cates AW, Wolf PD, Hillsley RE, Souza JJ, Smith WM, Ideker RE. The probability of defibrillation success and the incidence of postshock arrhythmia as a function of shock strength. PACE 1994;17:1208–1217PubMedGoogle Scholar
  53. 53.
    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. PACE 2000;23:807–817PubMedGoogle Scholar
  54. 54.
    Gold JH, Schuder JC, Stoeckle H, Granberg TA, Hamdani SZ, Rychlewski JM. Transthoracic ventricular defibrillation in the 100 kg calf with unidirectional rectangular pulses. Circulation 1977;56:745–750PubMedGoogle Scholar
  55. 55.
    Ding L, Splinter R, Knisley SB. Quantifying spatial localization of optical mapping using Monte Carlo simulations. IEEE Trans Biomed Eng 2001;48:1098–1107PubMedCrossRefGoogle Scholar
  56. 56.
    Hyatt CJ, Mironov SF, Vetter FJ, Zemlin CW, Pertsov AM. Optical action potential upstroke morphology reveals near-surface transmural propagation direction. Circ Res 2005;97:277–284PubMedCrossRefGoogle Scholar
  57. 57.
    Sharifov OF, Fast VG. Intramural virtual electrodes in ventricular wall: effects on epicardial polarizations. Circulation 2004;109:2349–2356PubMedCrossRefGoogle Scholar
  58. 58.
    Sharifov OF, Fast VG. Role of intramural virtual electrodes in shock-induced activation of left ventricle: optical measurements from the intact epicardial surface. Heart Rhythm 2006;3:1063–1073PubMedCrossRefGoogle Scholar
  59. 59.
    Sharifov OF, Ideker RE, Fast VG. High-resolution optical mapping of intramural virtual electrodes in porcine left ventricular wall. Cardiovasc Res 2004;64:448–456PubMedCrossRefGoogle Scholar
  60. 60.
    Cheek ER, Sharifov OF, Fast VG. Role of microscopic tissue structure in shock-induced activation assessed by optical mapping in myocyte cultures. J Cardiovasc Electrophysiol 2005;16:991–1000PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Vladimir G. Fast
    • 1
  1. 1.University of Alabama at BirminghamBirminghamUSA

Personalised recommendations