Title

The Ischemic Heart: Novel Research, Diagnostic, and Therapeutic Techniques

Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

Summer 9-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Igor I Efimov

Abstract

Sudden cardiac death (SCD) accounts for as many as ~400,000 deaths annually in the United States. The leading cause of SCD is ventricular fibrillation, which is almost always associated with the narrowing or occlusion of coronary arteries and ischemia. Despite our vast knowledge of the metabolic and electrophysiological changes that accompany ischemia, the exact mechanism triggering and sustaining ischemia-induced arrhythmias is not completely understood. A significant reduction in mortality has been achieved with implantable cardioverter defibrillators and drugs, such as beta-blockers. Unfortunately, many SCDs are caused by the first coronary event, leaving no opportunity for clinical intervention. Scientific research has vigorously attempted to elucidate the mechanism causing these ventricular arrhythmias in the hope of improving outcomes and saving lives. In this dissertation, we describe novel research, diagnostic, and therapeutic techniques to gain insight into the mechanism causing ischemia-induced arrhythmias and identify ways to improve treatment.

First, we developed an optical imaging system that simultaneously monitors mitochondrial function and sarcolemmal transmembrane potential. Monitoring mitochondrial function during ischemia at the whole-heart level has led to conflicting results; mitochondrial depolarization has been reported as slow and sporadic, and alternatively as a rapidly propagating unidirectional wave. Here, we resolve the aforementioned differences and determine the unknown relation between mitochondrial function and arrhythmogenesis in explanted rabbit hearts. In addition, we investigated the utility of stretchable-flexible electronics as a platform for monitoring metabolism and electrophysiology. We tested sensors and actuators integrated into 2-dimensional planar sheets, balloon catheters, and 3-dimensional epicardial socks that completely envelop the ventricles and show the diagnostic benefit of multiparametric monitoring of ischemia. Finally, an ablation strategy utilizing two common energy sources, cryothermy and radiofrequency, was assessed for improved lesion creation in beating human tissue. Ablation is an important therapeutic option to mitigate ventricular arrhythmias when an infarction is present. Here, we show that cryoablation followed by radiofrequency ablation enhances lesion depth compared to other energy source combinations. This approach has the potential to improve clinical outcomes in the treatment of ventricular tachycardia that might otherwise lead to ventricular fibrillation and sudden cardiac death.

DOI

https://doi.org/10.7936/K7HM56F9

Comments

This work is not available online per the author’s request. For access information, please contact digital@wumail.wustl.edu or visit http://digital.wustl.edu/publish/etd-search.html.

Permanent URL: http://dx.doi.org/10.7936/K7HM56F9

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