Low-energy defibrillation with nanosecond electric shocks

Abstract

Aims: Reliable defibrillation with reduced energy deposition has long been the focus of defibrillation research. We studied the efficacy of single shocks of 300 ns duration in defibrillating rabbit hearts as well as the tissue damage they may cause.

Methods and results: New Zealand white rabbit hearts were Langendorff-perfused and two planar electrodes were placed on either side of the heart. Shocks of 300 ns duration and 0.3-3 kV amplitude were generated with a transmission line generator. Single nanosecond shocks consistently induced waves of electrical activation, with a stimulation threshold of 0.9 kV (over 3 cm) and consistent activation for shock amplitudes of 1.2 kV or higher (9/9 successful attempts). We induced fibrillation (35 episodes in 12 hearts) and found that single shock nanosecond-defibrillation could consistently be achieved, with a defibrillation threshold of 2.3-2.4 kV (over 3 cm), and consistent success at 3 kV (11/11 successful attempts). Shocks uniformly depolarized the tissue, and the threshold energy needed for nanosecond defibrillation was almost an order of magnitude lower than the energy needed for defibrillation with a monophasic 10 ms shock delivered with the same electrode configuration. For the parameters studied here, nanosecond defibrillation caused no baseline shift of the transmembrane potential (that could be indicative of electroporative damage), no changes in action potential duration, and only a brief change of diastolic interval, for one beat after the shock was delivered. Histological staining with tetrazolium chloride and propidium iodide showed that effective defibrillation was not associated with tissue death or with detectable electroporation anywhere in the heart (six hearts).

Conclusion: Nanosecond-defibrillation is a promising technology that may allow clinical defibrillation with profoundly reduced energies.

Keywords: Defibrillation; Low-energy; Millisecond shocks; Nanosecond shocks; Stimulation.

Figure 1

Setup used in our defibrillation experiments. (A) Optical mapping setup. The heart is stained with the voltage-sensitive fluorescent probe Di-4-ANBDQBS and illuminated with a diffused laser at 671 nm. Fluorescent light is filtered with a long pass filter and recorded with a CCD camera. (B) Photograph of heart in setup. The electrodes are positioned to the left and to the right of the heart (see arrows labelled ‘El.’), illumination is from the top, and fluorescent light is also recorded from the top. Two aluminium plate electrodes touch the heart at the right and left ventricular free wall. Inset shows indium tin oxide (ITO) window electrode for observation of shock effects right under the electrode. A circular hole was drilled into the aluminium electrode and covered with glass that was coated with (electrically conductive) ITO. The label ‘asterisks’ indicates where the ITO electrode was located when it was used. The white rectangle indicates a typical field of view of the camera. (C) Spark gap generator for 300 ns shocks. (D) Experimentally determined shock waveform.

Figure 2

Stimulation of cardiac tissue with nanosecond shock (5 hearts). (A) Optical recording from a representative location on the cardiac surface. The heart is initially in sinus rhythm, before a single shock is applied at the time marked with a dashed line. Afterwards, sinus rhythm continues. (B) Activation map for sinus activation. (C) Activation map following nanosecond shock activation. (D) Stimulation success rate as a function of stimulus amplitude. Numbers in parentheses indicate how many observations contributed to each of the data points. Red line shows a sigmoidal function fitted to the data.

Figure 3

Defibrillation with nanosecond shock (12 hearts). (A) Optical recording from a representative surface location on the cardiac surface. The heart is initially fibrillating, before a single shock is applied at the time marked with a dashed line. After the shock, sinus rhythm is restored. (B) Defibrillation success rate as a function of stimulus amplitude. Numbers in parentheses indicate how many observations contributed to each of the data points. Red line shows a sigmoidal function fitted to the data. (C) Comparison of defibrillation for millisecond defibrillation (monophasic) and nanosecond defibrillation (2 hearts, see text for comparison with previous data regarding the energy threshold of millisecond defibrillation). Black empty circles indicate the threshold energies that we determined in individual hearts. Grey horizontal lines mark averages and standard error of the mean.

Figure 4

Mechanism of nanosecond defibrillation. Panels A–H show a series of snapshots of transmembrane voltage distribution, before (A, B), at (C), and after (D–H) the application of a nanosecond shock to a heart that exhibits re-entry. Dark areas are at resting transmembrane potential, bright areas are depolarized. White numbers in the lower right corner state the time the snapshot was taken, relative to the shock application (negative numbers mean that the snapshot was taken before the shock). White arrows indicate the direction of wave propagation.

Figure 5

Histological assessment of tissue damage after a single 300 ns, 3 kV shock. (A) Side-by-side view of TTC stains (left) and PI fluorescence imaging (right) for a series of four coronal sections of the heart, arranged from apex (top) to base (bottom). The grey vertical bars in the top left panel indicate the electrode positions. The PI fluorescence is so weak that cardiac tissue is hardly discernable. All images are oriented with the left ventricle on the right side of the image. (B) Positive control using a 50 μl Triton X-100 injection. Injection site is marked with a red arrow in both the TTC stain (top) and the PI fluorescence image (bottom).

Figure 6

Effect of nanosecond stimulation on action potential duration and diastolic interval (4 hearts). (A) Sample optical recording from cardiac surface to introduce our notation (DI_pre, APD_pre, APD_stim, DI_post, APD_post, and DI_post, 2). (B) Photograph of heart in setup, with superimposed positions of shock electrodes and sample locations for the evaluation of APD and DI. (C) Change of APD_stim (relative to APD_pre) as a function of electrode position for 4 hearts. Different symbols (‘inverted triangle’, ‘diam’, ‘open circle’, and ‘open square’) represent different hearts. (D) Change of APD_post (relative to APD_pre) as a function of electrode position for 4 hearts. (E) Change of DI_post (relative to DI_pre) as a function of electrode position for 4 hearts. (F) Change of DI_post, 2 (relative to DI_pre) as a function of electrode position for 4 hearts.

Figure 7

Effect of nanosecond defibrillation on diastolic interval (5 hearts). (A) Sample optical recording from cardiac surface to introduce our notation (DI_post, DI_post, 2, and DI_post, 3). (B) Change of DI_post (relative to DI_post, 2) as a function of electrode position for 5 hearts (same electrode positions as in Figure 6). Different symbols (‘inverted triangle’, ‘diam’, ‘open circle’, ‘open star’, and ‘open square’) represent different hearts. (C) Change of DI_post, 3 (relative to DI_post, 2) as a function of electrode position for 4 hearts.