Year of Publication

2002

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Graduate School

Department

Biomedical Engineering

First Advisor

Dr. Abhijit Patwardhan

Abstract

Spatio-temporal variation in activation rates during ventricular fibrillation (VF)provides insight into mechanisms of sustained re-entry during VF. This study had three objectives related to spatio-temporal dynamics in activation rates during VF.

The first objective was to quantify spatio-temporal variability in activation rates,that is, in dominant frequencies, computed from epicardial electrograms recorded during VF in swine. Results showed that temporally and spatially, dominant frequencies variedas much as 20% of the mean dominant frequency, and the mean dominant frequencies increased during first 30 sec of VF. These results suggest that activation rates are nonstationary during VF.

The second objective of the study was to develop a new stimulation protocol for quantifying restitution of action potential duration (APD) by independently controlling diastolic intervals (DI). A property of cardiac cells that determines spatio-temporal variability in dominant frequencies is restitution of APD, which relates APD to the previous DI. Independent control of DI permits explicit determination of the role of memory in restitution. Restitution functions quantified using mathematical models of activation and our stimulation protocol, showed significant hysteresis. That is, for adiastolic interval, the action potential durations were as much as 15% longer during periods when the DI were decreasing than when the DI were increasing. We verified the feasibility of implementing our protocol experimentally in isolated and perfused rat hearts with action potentials recorded using floating glass microelectrodes.

The third objective of our study was to verify that spatio-temporal variability in dominant frequencies during VF could be modified using spatially distributed pacing strength stimuli. Simulated VF was induced in 400x400 and 400x800 matrices of cells. Electrical function of cells was simulated using the Luo-Rudy model. Stimulators were arranged in the matrices such that there were 5 rows of line stimulators. Results showed that it was possible to modify activations in almost 54% of the area and to modify spatio-temporal variability in activation during VF into a desired pattern by the use of synchronized pacing from multiple sites. These results support further exploration of distributed stimulation approach for potential improvements in defibrillation therapy.

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