Electric pulse repetition rate: Sensitization and desensitization

Abstract

In most applications of electroporation in biology, medicine, and industry, the desired effect is achieved by the delivery of multiple pulses. The pulse repetition rate (PRR) is one of the key factors which determine the efficiency of such treatments. Despite intense research, the impact of PRR has not been fully understood and remains one of the most controversial topics. Depending on the endpoints and specific conditions, increasing the PRR may increase, decrease, or make no difference in the effects of an electric pulse (EP) treatment. This complexity results from a combination of physical factors and biological effects. Electric modeling has been widely employed to explain PRR effects, but even the most advanced models showed limited predictive power. Recently it has been reported that mammalian cells exposed to electric pulses become more sensitive to subsequent EP treatments, a phenomenon that has been called electrosensitization. The sensitized state typically develops within tens of seconds after the initial EP exposure and reaches a maximum within minutes. When the overall EP treatments are made long enough for sensitization to develop, their effects increase two- to threefold. Electrosensitization is engaged when the overall treatment duration is made sufficiently long, by either lowering the PRR or by splitting the complete treatment into fractions. Understanding the role of PRR is critical for tuning various electroporation-based technologies and treatments to achieve the highest efficiency.