Vascular smooth muscle cells ablation with endovascular nonthermal irreversible electroporation.
ABSTRACT To evaluate the effect of endovascular nonthermal irreversible electroporation (NTIRE) on blood vessels.
Specially made endovascular devices with four electrodes on top of inflatable balloons were used to apply electroporation pulses. Finite element simulations were used to characterize NTIRE protocols that would not induce thermal damage to treated tissues. Right iliac arteries of eight rabbits were treated with 90 NTIRE pulses. Angiograms were performed before and after the procedures. Arterial specimens were harvested at 7 and 35 days. Evaluation included hematoxylin and eosin, elastic von Giessen, and Masson trichrome stains. Immunohistochemistry of selected slides included smooth muscle actin (SMA), proliferating cell nuclear antigen, von Willebrand factor (VWF), and S-100 antigen.
At 7 days, all NTIRE-treated arterial segments displayed complete, transmural ablation of vascular smooth muscle cells (VSMC). At 35 days, similar damage to VSMC was noted. In most cases, the elastic lamina remained intact, and endothelial layer regenerated. Occasional mural inflammation and cartilaginous metaplasia were noted. After 5 weeks, there was no evidence of significant VSMC proliferation, with the dominant process being wall fibrosis with regenerated endothelium.
NTIRE can be applied in an endovascular approach. It efficiently ablates vessel wall within seconds and with no damage to extracellular structures. NTIRE has possible applications in many fields of clinical cardiology, including arterial restenosis and cardiac arrhythmias.
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ABSTRACT: Electroporation-based applications require the use of specific pulse parameters for a successful outcome. When recommended values of pulse parameters cannot be set, similar outcomes can be obtained by using equivalent pulse parameters. We determined the relations between the amplitude and duration/number of pulses resulting in the same fraction of electroporated cells. Pulse duration was varied from 150 ns to 100 ms, and the number of pulses from 1 to 128. Fura 2-AM was used to determine electroporation of cells to Ca(2+). With longer pulses or higher number of pulses, lower amplitudes are needed for the same fraction of electroporated cells. The expression derived from the model of electroporation could describe the measured data on the whole interval of pulse durations. In a narrower range (0.1-100 ms), less complex, logarithmic or power functions could be used instead. The relation between amplitude and number of pulses could best be described with a power function or an exponential function. We show that relatively simple two-parameter power or logarithmic functions are useful when equivalent pulse parameters for electroporation are sought. Such mathematical relations between pulse parameters can be important in planning of electroporation-based treatments, such as electrochemotherapy and nonthermal irreversible electroporation.IEEE transactions on bio-medical engineering 09/2011; 58(11):3279-88. · 2.15 Impact Factor