Feasibility of selective cardiac ventricular electroporation

Alan Sugrue, Vaibhav R Vaidya, Christopher Livia, Deepak Padmanabhan, Anas Abudan, Ameesh Isath, Tyra Witt, Christopher V DeSimone, Paul Stalboerger, Suraj Kapa, Samuel J Asirvatham, Christopher J McLeod, Alan Sugrue, Vaibhav R Vaidya, Christopher Livia, Deepak Padmanabhan, Anas Abudan, Ameesh Isath, Tyra Witt, Christopher V DeSimone, Paul Stalboerger, Suraj Kapa, Samuel J Asirvatham, Christopher J McLeod

Abstract

Introduction: The application of brief high voltage electrical pulses to tissue can lead to an irreversible or reversible electroporation effect in a cell-specific manner. In the management of ventricular arrhythmias, the ability to target different tissue types, specifically cardiac conduction tissue (His-Purkinje System) vs. cardiac myocardium would be advantageous. We hypothesize that pulsed electric fields (PEFs) can be applied safely to the beating heart through a catheter-based approach, and we tested whether the superficial Purkinje cells can be targeted with PEFs without injury to underlying myocardial tissue.

Methods: In an acute (n = 5) and chronic canine model (n = 6), detailed electroanatomical mapping of the left ventricle identified electrical signals from myocardial and overlying Purkinje tissue. Electroporation was effected via percutaneous catheter-based Intracardiac bipolar current delivery in the anesthetized animal. Repeat Intracardiac electrical mapping of the heart was performed at acute and chronic time points; followed by histological analysis to assess effects.

Results: PEF demonstrated an acute dose-dependent functional effect on Purkinje, with titration of pulse duration and/or voltage associated with successful acute Purkinje damage. Electrical conduction in the insulated bundle of His (n = 2) and anterior fascicle bundle (n = 2), was not affected. At 30 days repeat cardiac mapping demonstrated resilient, normal electrical conduction throughout the targeted area with no significant change in myocardial amplitude (pre 5.9 ± 1.8 mV, 30 days 5.4 ± 1.2 mV, p = 0.92). Histopathological analysis confirmed acute Purkinje fiber targeting, with chronic studies showing normal Purkinje fibers, with minimal subendocardial myocardial fibrosis.

Conclusion: PEF provides a novel, safe method for non-thermal acute modulation of the Purkinje fibers without significant injury to the underlying myocardium. Future optimization of this energy delivery is required to optimize conditions so that selective electroporation can be utilized in humans the treatment of cardiac disease.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Demonstration of location of the…
Fig 1. Demonstration of location of the catheters used for pulsed electric field delivery, with one catheter fixed in the coronary sinus and the other located at a Purkinje potential in the LV.
Fig 2
Fig 2
Two examples (A and B) of loss of Purkinje fiber electrical conduction after PEF delivery. Yellow arrow highlights the Purkinje potential.
Fig 3. Loss of small Purkinje potential,…
Fig 3. Loss of small Purkinje potential, but resistance of the His to PEF.
Fig 4. Reversible loss of a fascicular…
Fig 4. Reversible loss of a fascicular signal from PEF delivery.
Fig 5. Myocardial amplitude change after Pulsed…
Fig 5. Myocardial amplitude change after Pulsed Electric Field (PEF) delivery.
Fig 6. Histopathological slide showing damaged Purkinje…
Fig 6. Histopathological slide showing damaged Purkinje fibers outlines in black and the purple outline demarking an area of acute hemorrhage.

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