Surgical Ablation of Cardiac Tissue with Nanosecond Pulsed Electric Fields in Swine.

BACKGROUND: Myocardial tissue can be ablated by the application nanosecond pulsed fields (nsPEFs). The applied electric fields irreversibly permeabilize cell membranes and thereby kill myocytes while leaving the extracellular matrix intact. METHODS: In domestic pigs (n = 10), hearts were exposed via sternotomy and either ablated in vivo ([Formula: see text] = 5) or in excised, Langendorff-perfused hearts ([Formula: see text] = 5). The nsPEFs consisted of 6-36 pulses of 300 ns each, delivered at 3-6 Hz; the voltage applied varied from 10 to 12 kV. Atrial lesions were either created after inserting the bottom jaw of the bipolar clamp into the atrium via a purse string incision (2-3 lesions per atrium) or by clamping a double layer of tissue at the appendages (one lesion per atrium). Ventricular lesions were created after an incision at the apex. The transmurality of each lesion was determined at three points along the lesion using a triphenyl tetrazolium chloride (TTC) stain. RESULTS: All 27 atrial lesions were transmural. This includes 13/13 purse string lesions (39/39 sections, tissue thickness 2.5-4.5 mm) and 14/14 appendage lesions (42/42 sections, tissue thickness 8-12 mm). All 3 right ventricular lesions were transmural (9/9 sections, 18 pulses per lesion). Left ventricular lesions were always transmural for 36 pulses (3/3 lesions, 9/9 sections). All lesions have highly consistent width across the wall. There were no pulse-induced arrhythmias or other complications during the procedure. CONCLUSIONS: nsPEF ablation reliably created acute lesions in porcine atrial and ventricular myocardium. It has far better penetration and is faster than both radiofrequency ablation and cryoablation and it is free from thermal side effects.

Electroporation safety factor of 300 nanosecond and 10 millisecond defibrillation in Langendorff-perfused rabbit hearts.

AIMS: Recently, a new defibrillation modality using nanosecond pulses was shown to be effective at much lower energies than conventional 10 millisecond monophasic shocks in ex vivo experiments. Here we compare the safety factors of 300 nanosecond and 10 millisecond shocks to assess the safety of nanosecond defibrillation. METHODS AND RESULTS: The safety factor, i.e. the ratio of median effective doses (ED50) for electroporative damage and defibrillation, was assessed for nanosecond and conventional (millisecond) defibrillation shocks in Langendorff-perfused New Zealand white rabbit hearts. In order to allow for multiple shock applications in a single heart, a pair of needle electrodes was used to apply shocks of varying voltage. Propidium iodide (PI) staining at the surface of the heart showed that nanosecond shocks had a slightly lower safety factor (6.50) than millisecond shocks (8.69), p = 0.02; while PI staining cross-sections in the electrode plane showed no significant difference (5.38 for 300 ns shocks and 6.29 for 10 ms shocks, p = 0.22). CONCLUSIONS: In Langendorff-perfused rabbit hearts, nanosecond defibrillation has a similar safety factor as millisecond defibrillation, between 5 and 9, suggesting that nanosecond defibrillation can be performed safely.

Using Nanosecond Shocks for Cardiac Defibrillation.

The purpose of this review article is to summarize our current understanding of the efficacy and safety of cardiac defibrillation with nanosecond shocks. Experiments in isolated hearts, using optical mapping of the electrical activity, have demonstrated that nanosecond shocks can defibrillate with lower energies than conventional millisecond shocks. Single defibrillation strength nanosecond shocks do not cause obvious damage, but repeated stimulation leads to deterioration of the hearts. In isolated myocytes, nanosecond pulses can also stimulate at lower energies than at longer pulses and cause less electroporation (propidium uptake). The mechanism is likely electroporation of the plasma membrane. Repeated stimulation leads to distorted calcium gradients.

Excitation and injury of adult ventricular cardiomyocytes by nano- to millisecond electric shocks.

Intense electric shocks of nanosecond (ns) duration can become a new modality for more efficient but safer defibrillation. We extended strength-duration curves for excitation of cardiomyocytes down to 200 ns, and compared electroporative damage by proportionally more intense shocks of different duration. Enzymatically isolated murine, rabbit, and swine adult ventricular cardiomyocytes (VCM) were loaded with a Ca2+ indicator Fluo-4 or Fluo-5N and subjected to shocks of increasing amplitude until a Ca2+ transient was optically detected. Then, the voltage was increased 5-fold, and the electric cell injury was quantified by the uptake of a membrane permeability marker dye, propidium iodide. We established that: (1) Stimuli down to 200-ns duration can elicit Ca2+ transients, although repeated ns shocks often evoke abnormal responses, (2) Stimulation thresholds expectedly increase as the shock duration decreases, similarly for VCMs from different species, (3) Stimulation threshold energy is minimal for the shortest shocks, (4) VCM orientation with respect to the electric field does not affect the threshold for ns shocks, and (5) The shortest shocks cause the least electroporation injury. These findings support further exploration of ns defibrillation, although abnormal response patterns to repetitive ns stimuli are of a concern and require mechanistic analysis.

Low-energy defibrillation with nanosecond electric shocks.

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.