The role of damage in reversible electroporation optimization: theory and experiments in a vegetable model

MATÍAS MARINO; PABLO GIUNTA; ALEJANDRO SOBA; MATÍAS MARINO; PABLO GIUNTA; ALEJANDRO SOBA; NAHUEL OLAIZ; EMMANUEL LUJÁN; CECILIA SUAREZ; NAHUEL OLAIZ; EMMANUEL LUJÁN; CECILIA SUAREZ; SEBASTIÁN MICHINSKI; EZEQUIEL GOLDBERG; GUILLERMO MARSHALL; SEBASTIÁN MICHINSKI; EZEQUIEL GOLDBERG; GUILLERMO MARSHALL

TouLouse

Congreso; 3rd World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, and Food & Environmental Technologies; 2019

In electroporation (EP)-based protocols, such as in Gene Electrotransfer (GET), tissue pH-damage and ROS damage underline the EP phenomenon, however, tissue damage due to irreversible EP or thermal damage due to temperature effects may occur owing to the possible appearance of strong electric fields in a zone very close to the electrodes. In the quest of an optimal GET protocol, the concept of the dose-response relationship is addressed, with the objective of maximizing the desired treatment effect and minimizing collateral tissue damage. Previous theoretical predictions and experimental measurements for GET protocols show that a reliable dose parameter is the pulse dosage and reliable response parameters are the reversibly electroporated tissue and the unwanted damage due to pH. Here, we extend those results using a GET protocol model that combines an extension of the standard stationary EP model for predicting the reversibly electroporated tissue and damage due to irreversible EP, and the standard Electrolytic Ablation (EA) model for predicting damage due to pH, ROS and temperature. Theoretical predictions were confirmed by experimental measurements in a vegetable model (potato) consisting in the recording of the tissue damage due to pH and to irreversible EP and temperature variations during the treatment, and of the reversibly electroporated tissue (blackened area) 12 hours after the treatment. It was found that an optimal dose-response relationship in a GET protocol for different voltage to distance ratios and fixed pulse length and frequency is predicted as the critical pulse dosage yielding maximum reversibly electroporated tissue with minimum tissue damage due to pH, ROS, irreversible EP and temperature.