Multiple monophasic shocks improve electrotherapy of ventricular tachycardia in a rabbit model of chronic infarction

Abstract

Background: We previously showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase dependent when a single monophasic shock (1MP) is used.

Objective: The purpose of this study was to extend these findings to a biphasic shock (1BP) and to compare the efficacy of phase-independent multiple monophasic (5MP) and biphasic shocks (5BP).

Methods: Panoramic optical mapping with blebbistatin (5 microM) was performed in postmyocardial infarction rabbit hearts (n = 8). Flecainide (1.64 +/- 0.68 microM) was administered to promote sustained arrhythmias. 5MP and 5BP were applied within one VT cycle length (CL). Results were compared to 1BP and antitachycardia pacing.

Results: We observed monomorphic VT with CL = 149.6 +/- 18.0 ms. Similar to 1MP, CVTs of 1BP were found to be phase dependent, and the maximum versus minimum CVT was 8.6 +/- 1.7 V/cm versus 3.7 +/- 1.9 V/cm, respectively (P = .0013). Efficacy of 5MP was higher than that of 1BP and 5BP. CVT was 3.2 +/- 1.4 V/cm for 5MP versus 5.3 +/- 1.9 V/cm for 5BP (P = .00027). 5MP versus averaged 1BP CVT was 3.6 +/- 2.1 V/cm versus. 6.8 +/- 1.5 V/cm, respectively (P = .00024). Antitachycardia pacing was found to be completely ineffective in this model.

Conclusion: Maintenance of shock-induced virtual electrode polarization by multiple monophasic shocks over a VT cycle is responsible for unpinning of reentry leading to self-termination. Elimination of virtual electrode polarization by shock polarity reversal during multiple biphasic shocks proved ineffective. A significant reduction in CVT can be achieved by applying multiple monophasic shocks within one VT CL or one single shock at the proper coupling interval.

Conflict of interest statement

Conflict of Interest:

Dr. Efimov is a consultant to Cardialen Inc.

Figures

Figure 1

Initiation of a stable VT by multiple shock protocol. Top: Optical signal (purple) showing that a VT was induced by four monophasic shocks (red, 5 V/cm, 163 ms between each shock). Numbers 1–6 correspond to the time windows of activation maps 1–6 in the lower panels, respectively. Mid: Left panel is a digital photograph of the anterior view of the heart. Middle panel is the 2D unwrapped epicardium map. The solid line represents the septum. Infarct region is indicated with a dashed line. Right panel is a 2D unwrapped map of shock-induced VEP for a 5 V/cm 1MP. Bottom: Six successive activation maps show the process of the initiation of a stable reentrant circuit. Left column shows anterior view of 3D activation maps. Right column contains 2D unwrapped activation maps.

Figure 2

Two main morphologies of sustained stable VT in one heart. A. Photograph of anterior view of heart. Infarct region is white tissue from mid LV to apex. B. 3D phase maps of stable reentrant VTs rotated clockwise and anchored at IBZ. C. Lead I ECG during clockwise VT. This was the predominant VT morphology which appears at 56% inductions. The small peak that appeared every three beats indicates 3:1 retrograde excitation of atria during VT. D-F. Similar panels as A,B, and C only for a second primary VT morphology (22% inductions) which was counter-clockwise.

Figure 3

Termination of stable VT by 1BP applied at the proper phase. Heart and VT morphology correspond to Figure 1 and 2. Top: Optical action potential (blue) shows that VT terminated after 1BP (red, 4 V/cm, t=160 ms). Lower panels are 2D wrapped phase maps from t=0 to t=780 ms. Asterisks indicate shock-induced secondary sources. Arrows represent the directions of the wave front propagation.

Figure 4

Failure of cardioversion due to the improper application time of 1BP. This VT had the same morphology as that in Figure 3. Top: Optical action potential (blue) shows the cardioversion failure of a 1BP (red, 4 V/cm, t=266 ms). Lower panels are 2D wrapped phase maps.

Figure 5

Termination of stable VT with improper application time of cardioversion shock requires higher energy. This VT had the same morphology as previous figures. Top: Optical action potential (blue) showing that VT was terminated by 1 BP shock (red, 8 V/cm, t=281 ms). Lower panels are 2D wrapped phase maps.

Figure 6

Plot of the application phases of the shock versus CVTs with 1BP for the VTs with a same morphology. The application phase varied within one VT CL. Shock strength started with 1 V/cm and was increased by 1 V/cm until VT was terminated or the shock strength reached the maximum amplitude we could deliver (10 V/cm). The CVT varied greatly as a function of the application phase.

Figure 7

Termination of VT by 5MP applied within one VT CL. Top: Optical action potential (blue) shows that VT unpinned and self-terminated after application of 5MP (red, 4 V/cm, t=177 ms). The first panel below the optical trace is a VEP map measured from a 1MP shock (5V/cm) applied at the plateau-phase. The other panels are 2D unwrapped phase maps.

Figure 8

Destabilization of stable VT by 5BP. Top: Optical action potential (blue) shows that VT was destabilized after application of 5BP (red, 5 V/cm, t=213 ms). Lower panels are 2D wrapped phase maps. Termination of this VT was not recorded in this file. However, it self-terminated after approximately one minute.