High Frequency Electroporation: Pulsed Field Ablation with Minimal Muscle Contractions

Background: Irreversible electroporation (IRE) is a non-thermal ablation method that causes selective cell apoptosis by using short high-voltage pulses. IRE induces muscle contractions and therefore requires paralytics. This study investigated whether a novel modified IRE protocol of high-voltage high-frequency pulses (HF-EP) can be applied to the beating heart with minimal muscle contractions. Methods: 30 Sprague-Dawley rats were allocated to 3 different HF-EP protocols creating anterior myocardial damage using a previously described in-vivo open thoracotomy model. Protocols differed by frequency (100kHz, 150kHz) and number of pulses (20, 60). Study included a control group of 10 standard IRE monopolar pulses. All protocols used amplitude of 1100Vp-p and a two-needle configuration. Degree of muscle contraction during IRE application was evaluated qualitatively and documented with video. Animal were euthanized on day 14. Myocardial damage was evaluated by histological morphometric and computer-assisted analysis of the degree of fibrosis. Results: In contrast to the standard IRE protocol, all three HF-EP protocols were not associated with collateral muscle contractions (Supplementary Video). Standard IRE protocol was associated with significant damage as was predicted, based on previous studies. Compared to standard 10 monopolar electroporation pulses, 20 pulses of HF-EP of 100 and 150 kHz were associated with lesser extent of myocardial damage (infarct to healthy tissue fibrosis ratio of 27.5±11.2 vs. 12.8±9.4 and 7.44±2.1; p=.03 and ±11.2 vs. 19.44±4.23, p=.17; 25.10±12.6 vs. 19.42±8.18, p=.34; 23.38±8.3 vs. 32.90±19.33, p=.26, respectively). Conclusion: A novel high frequency IRE protocol can cause comparable myocardial damage without causing collateral muscle contractions. HF-EP holds the potential of becoming an alternative non-thermal method for heart ablation.