Toward Low Energy Defibrillation

The virtual electrode hypothesis of defibrillation has not only allowed for explanation of the basic mechanisms of defibrillation, but it is also allowing us to entirely rethink our approach to conventional defibrillation. Reentrant VT is often pinned or anchored at a functionally or anatomically heterogeneous region that comprises the core of reentry. The theory of virtual electrode polarization and the activating function predict that areas near the reentry core will experience greater polarization in response to an applied electric field compared to the surrounding, more homogeneous tissue. Thus, the core of reentry can be preferentially excited with very small electric fields to destabilize and unpin reentrant VT from its stationary core. However, the external field must be applied at precisely the right moment for the virtual electrode-induced excitation to properly interact with and terminate VT. This idea has been recently validated both in theory84 and in experiments.85'86

Takagi et al.84 demonstrated this concept in a two-dimensional bidomain model with a nonconductive circular obstacle comprising the core of reentry. Figure 11 shows a successful and nonsuccessful shock application. At t = 0 ms, a spiral wave (S) is shown anchored to the obstacle rotating counterclockwise. A 0.52V/cm—1 uniform external field is applied at

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Figure 10: Ascending versus descending ramp monophasic waveforms. (a) Schematic of experimental setup showing shock electrode locations (green lines), field of view (blue box), and locations of individual optical traces shown in (b) and (c) (blue and red lines). RA, right atrium; LA, left atrium. (b) Optical action potentials during shock application for ascending and descending ramp defibrillation waveforms. (c) AVm for the traces shown in (b). Ascending waveforms produce maximum polarization at shock end, whereas descending waveforms produce maximum polarization near the beginning of shock application. (d) Maps of polarization at shock end. (e) Voltage gradient at shock end. (f) Maps of postshock activation (Qu et al. 2005)83

Figure 10: Ascending versus descending ramp monophasic waveforms. (a) Schematic of experimental setup showing shock electrode locations (green lines), field of view (blue box), and locations of individual optical traces shown in (b) and (c) (blue and red lines). RA, right atrium; LA, left atrium. (b) Optical action potentials during shock application for ascending and descending ramp defibrillation waveforms. (c) AVm for the traces shown in (b). Ascending waveforms produce maximum polarization at shock end, whereas descending waveforms produce maximum polarization near the beginning of shock application. (d) Maps of polarization at shock end. (e) Voltage gradient at shock end. (f) Maps of postshock activation (Qu et al. 2005)83

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Figure 11: Bidomain simulations illustrating the low-energy "unpinning" concept. (a) Successful unpinning. t = 0 ms: spiral wave (S) is anchored to the obstacle rotating counterclockwise. t = 40 ms: a 0.52 V/cm—1 external field is applied. Positive and negative polarization (D+, D—) occur on opposite sides of the obstacle. t = 80 ms: the positive polarization results in a new wavefront (W), which rotates clockwise. t = 280 ms: the wavefronts collide resulting in detachment of both spiral waves. (b) An unsuccessful attempt due to improper timing of the applied field (Takagi et al. 2004)84

Figure 11: Bidomain simulations illustrating the low-energy "unpinning" concept. (a) Successful unpinning. t = 0 ms: spiral wave (S) is anchored to the obstacle rotating counterclockwise. t = 40 ms: a 0.52 V/cm—1 external field is applied. Positive and negative polarization (D+, D—) occur on opposite sides of the obstacle. t = 80 ms: the positive polarization results in a new wavefront (W), which rotates clockwise. t = 280 ms: the wavefronts collide resulting in detachment of both spiral waves. (b) An unsuccessful attempt due to improper timing of the applied field (Takagi et al. 2004)84

Figure 12: Low-energy unpinning in an isolated rabbit right ventricular free wall preparation. A 0.58 V/cm-1 shock is applied at t = 13.3 ms. Unpinning is similar to theoretical example presented in Fig. 11. See text for details (Ripplinger et al. 2006)85

t = 40 ms. Positive and negative polarization (D+, D-) can be seen on opposite sides of the obstacle. The positive polarization results in a new wavefront (W), which begins to rotate clockwise around the obstacle. Counterclockwise rotation of W is prevented due to refractory tissue in this direction. The wavefronts collide at t = 280 ms, which results in detachment of both spiral waves from the obstacle. The lower panels of Fig. 11 illustrate an unsuccessful attempt due to improper timing of the applied field. In this case, W can propagate in both directions and results in resetting of the spiral wave.

Our group recently validated this mechanism experimentally in a rabbit using isolated right ventricular preparation.85 Figure 12 shows a spiral wave rotating counterclockwise around a line of block indicated with a black line (panel 1). At t = 13.3ms, a 0.58 V/cm-1 external field is applied, creating a new wavefront that propagates in both directions around the line of block. The clockwise-propagating wavefront then collides with the existing spiral wave (panel 3) causing detachment from the core and termination at the tissue boundary (panels 4-5). The counterclockwise portion of the new wavefront eventually terminates upon hitting a refractory region (panel 6-7). Our experimental results in this model indicate that a 20-fold reduction in defibrillation energy may be obtained compared to conventional defibrillation. In a follow-up study, our group demonstrated a similar 20-fold reduction in defibrillation energy required to terminate sustained VT in a canine 4-day healed myocardial infarction model.86 This new low energy approach may provide a promising alternative to conventional high-energy defibrillation and may alleviate many of the side effects currently associated with strong electric shocks.

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