All ETDs from UAB

Advisory Committee Chair

Jack M Rogers

Advisory Committee Members

Vladimir G Fast

Cheryl R Killingsworth

Gregory P Walcott

Xincheng Yao

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

In healthy hearts, the synchronized spread of electrical activation drives contraction. To investigate the role of cardiac geometry in modulating normal and abnormal electrical rhythms, we stained cardiac tissues with a fluorescent, voltage sensitive dye and imaged activation patterns with fast video cameras (optical mapping). This work is presented in three projects. Computer modeling has shown that conduction velocity increases when fibers are bowed toward the oncoming wavefront and decreases when fibers are bowed in the opposite direction. In the first project, cultured monolayers of cardiac myocytes were optically mapped to experimentally verify the theoretical effect of fiber curvature on wavefront conduction velocity. In 24 cultures, fiber curvature produced a 3.5% change in transverse conduction velocity. This suggests that a substrate with significant regional variation in fiber geometry will conduct electrical impulses heterogeneously, which could influence the success or failure of conduction in situations where excitability is already marginal. In the second project, we investigated the role of native cardiac structure in arrhythmogenesis by initiating simple arrhythmias, consisting of one or two rotors, in ten perfused whole pig hearts. In 24 of 30 arrhythmias initiated in either the left or right ventricle, the interaction of the initial rotor's wavefront with its own refractory wake produced the first new rotor(s) of ventricular fibrillation at the anterior insertion of the right ventricle. We observed depressed conduction velocity at this site, which is likely due to local discontinuities in fiber orientation. This finding may guide development of new anti-arrhythmic therapies that stop VF initiation by preventing wavebreak at this site. To ensure a correspondence between cardiac tissue and photodetector pixels, optical mapping studies typically employ an electromechanical uncoupling agent to block contraction. However, these drugs also alter electrophysiology. In the third project, we developed a new technique to optically map beating hearts. Transmembrane potential was obtained from the fluorescence encircled by markers that were attached to the epicardium. Epicardial strain was computed from the computer-tracked marker trajectories. This new method permits optical mapping in the absence of electromechanical uncoupling agents, and could provide insight into many pathologies and therapies that involve electromechanical interactions.

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