Fundamental Study on the Effects of Irreversible Electroporation Pulses on Blood Vessels with Application to Medical Treatment
Background: Irreversible electroporation (IRE) is a biophysical phenomenon in which a series of electric field pulses selectively damages only the lipid bilayer of the cell membrane. This work is a fundamental study on the effect of IRE on blood vessels, evaluating the feasibility and efficiency of endovascular IRE to destroy vascular smooth muscle cells (VSMC) in the arterial wall.
Methods & Results: Time dependent finite-element simulations of the electric field and bio-heat transfer equations were used to analyze the electric field and the temporal behavior of the temperature due to electroporation pulses. The Henriques and Moritz thermal damage integral was used to demonstrate that an endovascular electrode geometry exists with which IRE pulses can be applied across the arterial wall with no thermal damage.
In-vitro experiments with VSMC compared different electroporation protocols in order to find the electric field threshold for efficient IRE. In-vivo experiments with rodents demonstrated for the first time that IRE can ablate the VSMC population of the arterial wall, and that the ablation persists at 28 days. By comparing eight different electroporation protocols it was demonstrated that best ablation efficiency can be achieved with 90 square direct current pulses of 100µs at a frequency of 4 Hz delivering electric field of 1,750 V/cm across the vessel wall. In addition, a separate experiment demonstrated that IRE attenuated neointimal formation in rodent carotid arteries evaluated 28 days following angioplasty damage.
In-vivo experiments with New-Zealand white rabbits evaluated the use of endovascular IRE. Using custom made endovascular devices with four longitudinal electrodes on top of an inflatable balloon, IRE was successfully applied to the vessel walls of eight iliac arteries. Independent pathology analysis confirmed the efficient ablation of the VSMC population evaluated at 7 and 35. In-vivo experiment with the same animal model using angioplasty damaged iliac arteries, showed that endovascular IRE attenuated neointimal formation and luminal loss 35 days following angioplasty.
Conclusions: Non-thermal IRE is an efficient cell ablation method that can be used in an endovascular minimally-invasive approach. It holds the potential to treat multiple clinical problems, in particular the problem of coronary restenosis and cardiac arrhythmias.