Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Maor, Elad; Ivorra, Antoni; Rubinsky, Boris

doi:10.1371/journal.pone.0004757

Cited by 137 publications

(99 citation statements)

References 36 publications

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“…We did not formally evaluate ventricular function with echocardiography or strain imaging or perform pathological analysis to assess the impact of IRE. In addition, although IRE is considered nonthermal60, 61, 62 at higher voltages (specifically, 2500 V), we cannot rule out the possibility of a local increase in temperature. Another major limitation also relates to the different conduction properties between the Krebs buffer as opposed to blood, and whether this can be extrapolated to the human is unclear and merits further study.…”

Section: Discussionmentioning

confidence: 98%

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability

Livia

Sugrue

Witt

et al. 2018

JAHA

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BackgroundThe Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation (IRE) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE.Methods and ResultsIn an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90‐μs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T‐wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250–833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV (P=0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J (P=0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J.ConclusionsOur study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

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Section: Discussionmentioning

confidence: 98%

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability

Livia

Sugrue

Witt

et al. 2018

JAHA

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“…While some small amount of heat may be created, the mechanism of cell death does not rely on heat formation, thus removing the need for high temperatures. The absence of a large thermal effect may allow direct treatment of vessels, where the muscular cell layer is destroyed but the structural integrity of the vessel is preserved, as has been demonstrated in prior studies 9, 10…”

Section: Introductionmentioning

confidence: 93%

Intrapulmonary Vein Ablation Without Stenosis: A Novel Balloon‐Based Direct Current Electroporation Approach

Witt

Sugrue

Padmanabhan

et al. 2018

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BackgroundCurrent thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period.Methods and ResultsInitial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present.ConclusionsIrreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.

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“…The phenomenon is considered to be a universal method and platform technology because all types of cells (animal, plant and microorganisms) are affected by electroporation (Miklavčič 2012). In fact, many electroporation-based applications have already been identified and developed, such as electrochemotherapy (ECT) of tumors , nonthermal irreversible ablation of tumors Maor et al 2009), gene therapy (Heller and Heller 2010), food preservation (Toepfl et al 2007) and others (Daugimont et al 2010;Gusbeth et al 2009;Ušaj et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software

et al. 2013

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Electroporation-based treatment combining high-voltage electric pulses and poorly permanent cytotoxic drugs, i.e., electrochemotherapy (ECT), is currently used for treating superficial tumor nodules by following standard operating procedures. Besides ECT, another electroporation-based treatment, nonthermal irreversible electroporation (N-TIRE), is also efficient at ablating deepseated tumors. To perform ECT or N-TIRE of deep-seated tumors, following standard operating procedures is not sufficient and patient-specific treatment planning is required for successful treatment. Treatment planning is required because of the use of individual long-needle electrodes and the diverse shape, size and location of deepseated tumors. Many institutions that already perform ECT of superficial metastases could benefit from treatmentplanning software that would enable the preparation of patient-specific treatment plans. To this end, we have developed a Web-based treatment-planning software for planning electroporation-based treatments that does not require prior engineering knowledge from the user (e.g., the clinician). The software includes algorithms for automatic tissue segmentation and, after segmentation, generation of a 3D model of the tissue. The procedure allows the user to define how the electrodes will be inserted. Finally, electric field distribution is computed, the position of electrodes and the voltage to be applied are optimized using the 3D model and a downloadable treatment plan is made available to the user.

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Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Cited by 137 publications

References 36 publications

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability

Intrapulmonary Vein Ablation Without Stenosis: A Novel Balloon‐Based Direct Current Electroporation Approach

Planning of Electroporation-Based Treatments Using Web-Based Treatment-Planning Software

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