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Advisory Committee Chair

Jack M Rogers

Advisory Committee Members

Vladimir G Fast

Matthew W Kay

Andrew E Pollard

Gregory P Walcott

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Sudden cardiac arrest is a leading cause of death in the world. One of the common causes of sudden cardiac arrest is acute regional ischemia due to coronary occlusion. However, the mechanism of arrhythmia onset in this setting is still unclear. Previous stud-ies suggest that abnormal mechanical stretch during acute regional ischemia may play a role in initiating arrhythmia through triggering ectopic electrical activation. Optical map-ping has been widely used in cardiac electrophysiological research in the past decades. Compared with conventional electrical mapping techniques, optical mapping offers a number of advantages. But a major limitation of optical mapping is that optical signals are sensitive to tissue motion and thus cardiac contraction has to be arrested, usually by using excitation-contraction uncoupling agents during the experiments. Recent studies demonstrate that arresting cardiac contraction may alter the subject to be studied. Im-portantly, arresting cardiac contraction precludes the study of cardiac electrical-mechanical interaction. There are two major parts in this project: first, we developed a new optical map-ping system that can acquire signals from beating heart preparations without the need for suppressing contraction. This new system enables the simultaneous recording of cardiac mechanical deformation and electrical activity, thus providing a more complete view on cardiac electrical-mechanical interaction. In the second part of this project, we used the new optical mapping system to investigate the potential links between abnormal mechan-ical stretch and the onset of ectopic electrical activation during the early stages of acute regional ischemia in isolated heart models. In addition, we evaluated the utility of a stretch-activated ion channel blocker as a potential experimental tool for probing cardiac electrical-mechanical interaction in isolated pig hearts. The ultimate goal of this project is to improve our understanding of the mechanisms of arrhythmia onset in early-stage acute regional ischemia and to suggest improvements in prevention and treatment protocols.

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