Coronary heart disease is the single largest cause of mortality in the United States. Approximately 335,000 people die annually from sudden cardiac death, and the majority of these cases are believed to be from ventricular fibrillation. To effectively treat and prevent cardiac rhythm disturbances, the response of the heart to electrical stimulation must be understood. Although cardiac defibrillation therapy is an invaluable medical procedure, the mechanisms by which strong electrical shocks terminate potentially lethal fibrillation are still debated.
Bidomain models of cardiac tissue successfully characterize many of the effects of electrical stimulation of the heart. In the bidomain, the intracellular and extracellular spaces are distinct and have differing electrical anisotropies. With unequal anisotropy ratios, bidomain theory predicts simultaneous positive and negative polarization in response to stimulation, in the form of virtual cathodes and anodes that lead to interesting cardiac activation dynamics.
This research examined experimentally the response of cardiac tissue to electrical stimulation from a bidomain perspective. Changes in transmembrane potential during and following electrical stimulation were recorded optically using a voltage-sensitive fluorescent dye. Optical mapping allows noninvasive measurement with high spatiotemporal resolution and avoids electrical stimulus artifacts. We found that:
1. During unipolar anodal stimulation of diastolic tissue, the mechanism of excitation depends upon the extracellular potassium concentration.
2. With proper timing of unipolar stimulation close to refractoriness, damped waves with diminished amplitude and velocity either gradually die or sharply increase in amplitude after a delay to become a steadily propagating wave.
3. We confirmed bidomain model predictions that virtual electrodes from unipolar stimulation affect excitability through the cardiac cycle as shown by strength-interval curves.
4. Field stimulation of the diastolic heart revealed that increasing shock strength and duration do not necessarily result in faster activation because of virtual anode polarization.
5. Alternating regions of positive and negative virtual electrode polarization around an insulating heterogeneity occur during field stimulation and may affect plunge electrode measurements.
An increased understanding of how cardiac tissue responds to electrical stimulation in various conditions will guide improvements in treatment and prevention of cardiac rhythm disorders.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11232005-142052 |
| Date | 06 December 2005 |
| Creators | Woods, Marcella Cherie |
| Contributors | John P. Wikswo, Robert L. Galloway, Richard A. Gray, Michael I. Miga, Richard G. Shiavi |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11232005-142052/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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