The effect of high frequency electric pulses on muscle contractions and antitumor efficiency in vivo for a potential use in clinical electrochemotherapy

Muscle contractions present the main source of unpleasant sensations for patients undergoing electrochemotherapy. The contractions are a consequence of high voltage pulse delivery. Relatively low repetition frequency of these pulses (1 Hz) results in separate muscle contractions associated with each single pulse that is delivered. It would be possible to reduce the number of unpleasant sensations by increasing the frequency of electric pulses above the frequency of tetanic contraction, provided that the antitumor efficiency of electrochemotherapy remains the same. These assumptions were investigated in the present paper by measuring the muscle torque at different pulse repetition frequencies and at two different pulse amplitudes in rats and studying the antitumor efficiency of electrochemotherapy at different pulse repetition frequencies on tumors in mice. Measurements of muscle torque confirmed that pulse frequencies above the frequency of tetanic contraction (>100 Hz) reduce the number of individual contractions to a single muscle contraction. Regardless of the pulse amplitude, with increasing pulse frequency muscle torque increases up to the frequency of 100 or 200 Hz and then decreases to a value similar to that after application of a 1 Hz pulse train. Electrochemotherapy in vivo with higher repetition frequencies inhibits tumor growth and is efficient at all pulse frequencies examined (1 Hz-5 kHz). These results suggest that there is a considerable potential for clinical use of high frequency pulses in electrochemotherapy.