Date of Award

Fall 2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

Committee Director

Christian Zemlin

Committee Member

Barbara Hargrave

Committee Member

Michel Audette

Committee Member

Andre Pakhomov

Committee Member

Dean Krusienski

Abstract

In this thesis, we present new engineering approaches to several important cardiac diseases. Chapter 1 considers the dynamics of arrhythmias. The most dangerous arrhythmias are reentrant arrhythmias, including ventricular fibrillation and ventricular tachycardia. During these arrhythmias, there are one or several rotating excitation waves present in the heart. Because of their shape, these waves are called scroll waves; their center of rotation is a one-dimensional curve called the filament. Filaments largely constrain the configuration of a scroll wave but are much simpler, so much effort has gone into describing scroll wave dynamics in terms of the dynamics of their filaments. In particular, the “geodesic principle” for filaments, which says that stable filaments are geodesics in a metric derived from the diffusivity, has been proposed and established for certain restrictive conditions. In this project, we show that the geodesic principle applies much more broadly, including for very large filament curvatures. We also discuss under which conditions the geodesic principle fails, particularly the case that the filament gets close to very heterogeneous substrate.

Chapters 2-4 introduce a new approach to cardiac defibrillation. The only existing effective treatment to ventricular fibrillation is to deliver high-energy electric shocks to the heart using a defibrillator to terminate fibrillation and restore organized rhythm. Defibrillators currently available are effective in treating ventricular fibrillation, however, because of the large amount of energy deposited during the treatment can cause damaging effects to the tissue. In this project, we present results of a new technology using nanosecond pulsed electric fields to defibrillate the heart, while depositing only a fraction of energy needed by conventional defibrillators.

In the final part of this thesis, Chapters 5-7, we present results of an injectable therapeutic agent to regenerate the myocardium (heart muscle) affected by infarction. Myocardial infarction is a serious coronary artery disease that occurs when a coronary artery is so severely blocked that there is a dramatic reduction or complete disruption of blood supply, causing damage or death to the territory of the myocardium that was supplied by the blocked coronary vessel. Our results show how the injection of the therapeutic agent helps in preserving the electrical activity in the affected area, and also reduces pathological effects on the ejection fraction and heart rate.

In summary, we contribute to the understanding of the mechanisms of reentrant arrhythmias, develop new technology for ventricular defibrillation, and test a therapeutic agent for myocardial infarction.

ISBN

9781339503004

Available for download on Wednesday, April 18, 2018

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