Irreversible Electroporation Pulses Research Articles

A Novel Nonthermal Energy Source for Surgical Epicardial Atrial Ablation: Irreversible Electroporation

All currently used energy sources in surgical ablation for atrial fibrillation create lesions via thermal injury. We report for the first time the in vivo results of a new nonthermal modality of epicardial atrial ablation called irreversible electroporation (IRE). IRE utilizes a sequence of electrical pulses that produce permanent nonthermal damage to tissue in a few seconds with sharp borders between affected and unaffected regions. Five pigs underwent beating heart surgical epicardial ablations of their right and/or left atrial appendages, utilizing a sequence of 8, 16, or 32 direct current pulses of 1500 to 2000 V, 100 micros each, at a frequency of 5 per second, applied between two 4-cm long parallel electrodes with an IRE pulse generator. Local temperature measurements were performed during ablations followed by electrical isolation testing by pacing. Animal hearts were excised 24 hours after surgery and processed histologically to evaluate the degree of myocardial tissue necrosis and transmurality. A clear demarcation line between ablated and normal tissue, with no tissue disruption or charring, was observed on gross inspection of all lesions. Staining results showed complete transmural destruction of atrial tissue at the site of the electrode application in all 10 atrial lesions, measuring a mean of 0.9 cm in depth. Each 3- to 3.5-cm long lesion was created in 1 to 4 seconds with no local temperature change and with demonstration of electrical isolation. We propose a new modality to perform atrial ablations, which holds the potential of providing very swift, precise, and complete transmurality with no local heating effects.

In Vivo Results of a New Focal Tissue Ablation Technique: Irreversible Electroporation

This paper reports results of in vivo experiments that confirm the feasibility of a new minimally invasive method for tissue ablation, irreversible electroporation (IRE). Electroporation is the generation of a destabilizing electric potential across biological membranes that causes the formation of nanoscale defects in the lipid bilayer. In IRE, these defects are permanent and lead to cell death. This paper builds on our earlier theoretical work and demonstrates that IRE can become an effective method for nonthermal tissue ablation requiring no drugs. To test the capability of IRE pulses to ablate tissue in a controlled fashion, we subjected the livers of male Sprague-Dawley rats to a single 20-ms-long square pulse of 1000 V/cm, which calculations had predicted would cause nonthermal IRE. Three hours after the pulse, treated areas in perfusion-fixed livers exhibited microvascular occlusion, endothelial cell necrosis, and diapedeses, resulting in ischemic damage to parenchyma and massive pooling of erythrocytes in sinusoids. However, large blood vessel architecture was preserved. Hepatocytes displayed blurred cell borders, pale eosinophilic cytoplasm, variable pyknosis and vacuolar degeneration. Mathematical analysis indicates that this damage was primarily nonthermal in nature and that sharp borders between affected and unaffected regions corresponded to electric fields of 300-500 V/cm.