High frequency irreversible electroporation (H-FIRE) as a novel method of targeted cell death.

Abstract

277 Background: Irreversible electroporation unlike ablation is excellent in inducing cell death via apoptosis. It, however, has disadvantages of electrical conduction via cardiac and nervous tissue. This results in requiring cardiac monitoring and general anesthesia and paralytics while performing electroporation. We hypothesized a novel high-frequency IRE (H-FIRE) system employing ultra-short bipolar pulses would obviate the need for cardiac synchronization and paralytics while maintaining measurable effect on cell death. Methods: Female swine (55-65Kg) were used. Two H-FIRE electrodes were inserted into the liver (1.5-cm spacing). In the absence of paralytics H-FIRE pulses were delivered (2250V, 2-5-2 pulse configuration) at different on times (100 vs. 200μs) or number of pulses (100 vs. 300). Next electrodes were placed across major hepatic vascular structures and H-FIRE performed. At conclusion tissue was resected and analyzed histologically. Results: 24 H-FIREs were performed (mean ablation time 275 secs). No EKG abnormalities or changes in vital signs were measured during H-FIRE procedures. In 1/24 H-FIREs minor twitching of the rectus abdominis was recorded coinciding with pulse delivery. Histologically, tissues had effective electroporation as evidenced by cell death and caspase activity. Blinded scoring was performed for necrosis and apoptosis. Areas of cell death were predictable. No significant vascular damage or coagulated/thermally-desiccated blood was detected within major vessels following H-FIRE. Conclusions: H-FIRE is a novel way of liver electroporation. It produces predictable cell apoptosis without the requirement of paralytics and alteration of electrocardiographic signals as compared to traditional electroporation, while preserving underlying vascular integrity. Its application in cancer cell death needs to be further studied, but it has a potential for clinical use in targeting tumors with minimal morbidity and associated cardiac and neurologic side effects.