Abstract
BackgroundIrreversible electroporation (IRE) is a non-thermal cell ablation approach that induces selective damage to cell membranes only. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization.MethodsForty-two Sprague-Dawley rats were used to compare myocardial damage of seven different IRE protocols with anterior myocardial infarction damage. An in-vivo open thoracotomy model was used, with two-needle electrodes in the anterior ventricular wall. IRE protocols included different combinations of pulse lengths (70 vs. 100 μseconds), frequency (1, 2, 4 Hz), and number (10 vs. 20 pulses), as well as voltage intensity (50, 250 and 500 Volts). All animals underwent baseline echocardiographic evaluation. Degree of myocardial ablation was determined using repeated echocardiography measurements (days 7 and 28) as well as histologic and morphometric analysis at 28 days.ResultsAll animals survived 28 days of follow-up. Compared with 50V and 250V, electroporation with 500V was associated with significantly increased myocardial scar and reduction in ejection fraction (67.4%±4% at baseline vs. 34.6%±20% at 28 days; p <0.01). Also, compared with pulse duration of 70 μsec, pulses of 100 μsec were associated with markedly reduced left ventricular function and markedly increased relative scar area ratio (28%±9% vs. 16%±3%, p = 0.02). Decreasing electroporation pulse frequency (1Hz vs. 2Hz, 2Hz vs. 4Hz) was associated with a significant increase in myocardial damage. Electroporation protocols with a greater number of pulses (20 vs. 10) correlated with more profound tissue damage (p<0.05). When compared with myocardial infarction damage, electroporation demonstrated a considerable likeness regarding the extent of the inflammatory process, but with relatively higher levels of extra-cellular preservation.ConclusionsIRE has a graded effect on the myocardium. The extent of ablation can be controlled by changing pulse length, frequency and number, as well as by changing electric field intensity.
Highlights
Electroporation is a biophysical phenomenon in which cell membrane permeability to ions and molecules increases significantly in response to externally applied short pulses of direct current electric fields
Compared with 50V and 250V, electroporation with 500V was associated with significantly increased myocardial scar and reduction in ejection fraction (67.4%±4% at baseline vs. 34.6%±20% at 28 days; p
Compared with pulse duration of 70 μsec, pulses of 100 μsec were associated with markedly reduced left ventricular function and markedly increased relative scar area ratio (28%±9% vs. 16% ±3%, p = 0.02)
Summary
Electroporation is a biophysical phenomenon in which cell membrane permeability to ions and molecules increases significantly in response to externally applied short pulses of direct current electric fields. When the electric field applied is of relatively strong intensity, it may induce persistent change in membrane permeability and lead to cellular death. This process is called irreversible electroporation (IRE) and is an emergent non-thermal cell ablation modality that is increasingly used clinically to treat solid tumors [1,2,3]. Due to its simplicity of use, its non-thermal nature, and its ability not to damage extra-cellular components such as blood vessels [8,9,10], it is being evaluated in pre-clinical studies as a new approach for cardiovascular tissue ablation [11,12,13]. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization
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