The electric field of the same strength parallel to the skeletal muscle fibers caused more dye uptake and accordingly, a greater extent of electroporation of cells than when applied perpendicularly. It was shown experimentally in vitro and in vivo as well as numerically that with eight 100 µs long pulses, electroporation threshold depends on muscle orientation 31, 32. In these treatments, electric pulses are applied to muscle cells, which are typically elongated and oriented. Two clinically relevant treatments with electroporation are gene electrotransfer of skeletal muscles 19, 20, for example for DNA vaccination 21 against HIV, human papillomaviruses, influenza 22– 25, and cardiac ablation of cardiomyocytes in treatment of heart arrhythmias 26– 30. Electroporation is used in medicine 3 (electrochemotherapy 4– 6, gene electrotransfer 7, 8, transdermal drug delivery 9, irreversible electroporation as a method of tumor tissue ablation 10, 11, electrophysiology/cardiac ablation 12– 14), food technology 15, 16, and biotechnology 17, 18. If the cells do not recover and they die, it is considered as irreversible electroporation. If cells recover after electroporation, it is considered as reversible electroporation. Cell membrane permeability increases, presumably due to pore formation 2. When short, high voltage pulses are applied to biological membranes, cell electroporation occurs 1.
Using pulses of a few microseconds lends itself as a new possible strategy in achieving homogeneous electroporation in tissue with elongated cells of different orientation (e.g. In the range of a few microseconds, cells of both orientations were electroporated to the same extent. Results showed that cell orientation affects electroporation extent: using short, nanosecond pulses, cells perpendicular to electric field are significantly more electroporated than parallel (up to 100-times more pores formed), and with long, millisecond pulses, cells parallel to electric field are more electroporated than perpendicular (up to 1000-times more pores formed). Experimentally detected electroporation (evaluated separately for cells parallel and perpendicular to electric field) via Ca 2+ uptake in H9c2 and AC16 cardiomyocytes was numerically modeled using the asymptotic pore equation. We investigated how cell orientation influences electroporation with respect to different pulse durations (ns to ms range), both experimentally and numerically. Orientation of cells in electric field has been reported to affect electroporation, and hence electrodes placement and pulse parameters choice in treatments for achieving homogeneous effect in tissue is important. In gene electrotransfer and cardiac ablation with irreversible electroporation, treated muscle cells are typically of elongated shape and their orientation may vary.
Experimentally detected electroporation (evaluated separately for cells parallel and perpendicular to electric field) via Ca2+ uptake in H9c2 and AC16 cardiomyocytes was numerically modeled using the asymptotic pore equation.
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