The Effects of Interphase and Interpulse Delays and Pulse Widths on Induced Muscle Contractions, Pain and Therapeutic Efficacy in Electroporation-Based Therapies

Aleksandra Cvetkoska, Alenka Maček-Lebar, Tamara Polajžer, Matej Reberšek, Weston Upchurch, Paul A. Iaizzo, Daniel C. Sigg, Damijan Miklavčič

Research output: Contribution to journalArticlepeer-review

Abstract

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation’s efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation.

Original languageEnglish (US)
Article number490
JournalJournal of Cardiovascular Development and Disease
Volume10
Issue number12
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • atrial fibrillation
  • electroporation
  • nerve and muscle stimulation
  • pulse parameters
  • pulse waveform
  • pulsed-field ablation

PubMed: MeSH publication types

  • Journal Article

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