Effects of reversible and irreversible electroporation on endothelial cells and tissue blood flow

Abstract

Electroporation/electropermeabilization (EP), achieved by application of electric pulses to cells or tissues, induces reversible permeabilization of cell membranes under suitable conditions, thus facilitating entry of exogenous molecules into cells. If excess pulses are applied, and the cell cannot recover, this leads to irreversible electroporation (IRE). EP and IRE of tissues in humans are feasible, efficient, and tolerable, and its most advanced routine clinical uses are electrochemotherapy (ECT), where cytotoxic drugs are delivered to cells to treat tumors and nonthermal ablation of tumors with IRE. Also, reversible EP is gaining momentum as an efficient method for gene electrotransfer and DNAvaccination. The use of IRE, where the application of electric pulses results in the creation of a tissue lesion without a dependence on thermal processes or the requirement of adjuvant drugs, is currently intensively researched for treatment of various types of cancer. When EP, either reversible or irreversible, is applied to tissues in vivo or in patients, it also has tissue-specific effects. It was shown that EP affects the vasculature in tumors and in normal tissues such as muscle and skin. Application of reversible EP pulses increases the permeability of affected blood vessels, causes a transient vascular lock, i.e., decrease in perfusion, and modulates thediameter of affected blood vessels. Similarly, IRE increases the permeability of the affected blood vessels. Both IRE and reversible EP preserve the normal function of affected blood vessels in the long term which is important when they are used in well-perfused organs such as the liver or brain.