The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Background. In electrochemotherapy (ECT), chemotherapeutics are first administered, followed by short 100 mu s monopolar pulses. However, these pulses cause pain and muscle contractions. It is thus necessary to administer muscle relaxants, general anesthesia and synchronize pulses with the heart rhythm of the patient, which makes the treatment more complex. It was suggested in ablation with irreversible electroporation, that bursts of short high-frequency bipolar pulses could alleviate these problems. Therefore, we designed our study to verify if it is possible to use high-frequency bipolar pulses (HF-EP pulses) in electrochemotherapy. Materials and methods. We performed in vitro experiments on mouse skin melanoma (B16-F1) cells by adding 1-330 mu M cisplatin and delivering either (a) eight 100 mu s long monopolar pulses, 0.4-1.2 kV/cm, 1 Hz (ECT pulses) or (b) eight bursts at 1 Hz, consisting of 50 bipolar pulses. One bipolar pulse consisted of a series of 1 mu s long positive and 1 mu s long negative pulse (0.5-5 kV/cm) with a 1 mu s delay in-between. Results. With both types of pulses, the combination of electric pulses and cisplatin was more efficient in killing cells than cisplatin or electric pulses only. However, we needed to apply a higher electric field in HF-EP (3 kV/cm) than in ECT (1.2 kV/cm) to obtain comparable cytotoxicity. Conclusions. It is possible to use HF-EP in electrochemotherapy; however, at the expense of applying higher electric fields than in classical ECT. The results obtained, nevertheless, offer an evidence that HF-EP could be used in electrochemotherapy with potentially alleviated muscle contractions and pain.