Date of Award

Spring 5-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical & Computer Engineering

Program/Concentration

Biomedical Engineering

Committee Director

Shu Xiao

Committee Member

Christian Zemlin

Committee Member

Andrei Pakhomov

Committee Member

Thomas Vernier

Abstract

Surgical ablation of cardiac tissue is the definitive treatment for the most common arrhythmia, atrial fibrillation. In current medical practice, myocardial tissue is often ablated by the application of radiofrequency (RF) currents which are delivered through an electrode to create lesions that block the electrical pathways that sustain reentrant arrhythmias and restore the normal heart rhythm. An alternative to RF is cryoablation, during which the endocardial or epicardial tissue is brought in contact with a cryoprobe. Both RF ablation and cryoablation have significant limitations. In RF ablation, tissue is heated in order to ablate it, but it is an open question how many applications are necessary to guarantee a transmural lesion. Cryoablation requires significant application times to reliably achieve transmurality and sometimes leads to unintended collateral tissue ablation including phrenic nerve injury. Given these limitations of thermal ablation, it is appropriate to consider alternatives.

An emerging technique used to ablate tissues is to apply a series of very short duration (nanoseconds) pulses at very high field strength (kV/cm) via electrodes capable of inducing a rapid change of transmembrane potential to the target tissue1. Our group performed an acute study which addressed the limitation of the thermal ablation and demonstrated that transmural lesions can be created within a few seconds by applying a nsPEF2. As part of my dissertation, we performed a chronic study regarding the cardiac tissue ablation with nsPEF in pigs that demonstrated that lesions created with nanosecond ablation mature and remain transmural over a period of at least six months.

Nanosecond shocks can also be used to excite nerve, muscle cells and cardiomyocytes, and could be used as an alternative mode of cardiac pacing and defibrillation in cardiac cells3–6 or for non-invasive nerve electrostimulation7. An interesting property of nanosecond stimulation is that it is in some situations more effective than expected from theory. The strength-duration curve would have slope -1 in a log-log plot and that is indeed observed in nerve8. However, that same slope is between -0.5 and -0.75 (from ms to ns range), in neurons and cardiomyocytes9–11. That implies that short, strong pulses are more effective at charging the membrane in cardiomyocytes.

To investigate this excess efficacy of nanosecond stimulation in cardiomyocytes, a modeling framework was developed. It describes the different electrical mechanisms that contribute to cell activation and allows us to study how these mechanisms affect the strength-duration curve. An investigation into electroporation and resealing that can occur in cardiomyocytes during nanosecond stimulation explains the lower than expected electric field necessary to activate cardiomyocytes. In particular, the electroporation due to the nsPEF delivery, prolongs the depolarization allowing the sodium current to activate even longer after the pulse ended.

The standard way of applying cryoablation is to the endocardium, but a substantial number of cardiac surgeons also perform epicardial cryoablation, which is convenient because it does not require an incision into the cardiac wall. To understand if this procedure consistently creates transmural lesions, we created epicardial cryolesions in a pig model under conditions that closely resemble those of human cardiac surgery and analyzed the quality of the lesions to test the efficacy of the procedure.

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DOI

10.25777/n961-yq88

ISBN

9798379735326

ORCID

0009-0007-5351-8283

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Available for download on Tuesday, June 25, 2024

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