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

MATÍAS MARINO; NAHUEL OLAIZ; FELIPE MAGLIETTI; SEBASTIÁN MICHINSKI; PABLO GIUNTA; EMMANUEL LUJÁN; EZEQUIEL GOLDBERG; ALEJANDRO SOBA; CECILIA SUÁREZ; 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 electricfields 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 theobjective of maximizing the desired treatment effect and minimizing collateral tissue damage. Previous theoretical predictions and experimentalmeasurements for GET protocols show that a reliable dose parameter is the pulse dosage and reliable response parameters are the reversibly electroporatedtissue and the unwanted damage due to pH. Here, we extend those results using a GET protocol model that combines an extension of the standardstationary EP model for predicting the reversibly electroporated tissue and damage due to irreversible EP, and the standard Electrolytic Ablation (EA) modelfor 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 thereversibly electroporated tissue (blackened area) 12 hours after the treatment. It was found that an optimal dose-response relationship in a GET protocol fordifferent voltage to distance ratios and fixed pulse length and frequency is predicted as the critical pulse dosage yielding maximum reversibly electroporatedtissue with minimum tissue damage due to pH, ROS, irreversible EP and temperature.