Effects of Electrochemotherapy on Microcirculatory Vasomotion in Tumors

Abstract

Electrochemotherapy (ECT) is a potent anti-tumor therapy with excellent results demonstrated in experimental and clinical studies. ECT consists of an injection of a chemotherapeutic drug (bleomycin or cisplatin) followed by an application of a series of short high-voltage electric pulses locally to the tumor mass. Antitumor effectiveness of ECT is attributed largely to increased cytotoxicity of the drug due to transient electroporation (EP) of tumor cells’ membranes, which facilitates an increased uptake of the drug by tumor cells. However, two additional mechanisms have been recognized as critical for complete eradication of treated tumors: the role of the host’s immune system and the vascular disrupting effect of ECT. Application of electric pulses to tumors is followed by rapid and profound reduction of tumor blood flow. Some minor reperfusion takes place within an hour after the treatment. By using laser Doppler flowmetry for continuous monitoring of tumor blood flow we provide evidence that in addition to the baseline blood flow changes, application of electric pulses and/or chemotherapeutic drug bleomycin also induces significant changes in vasomotional activity in tumor microcirculation within the first hour after treatment. Vasomotion is a collective term describing low-frequency (e.g. <0.5 Hz) fluctuations in local microcirculation as a result of cycles of contraction and relaxation of smooth microvascular musculature brought about by different physiological sources. The observed changes in vasomotion in tumors after EP and ECT support the hypotheses about the mechanisms of blood flow-modifying effects of electric pulses suggested in other studies.