Transmembrane Potential Mapping of Defibrillation

Figure 1: Diagram of the method used to record action potentials from the epicardium of isolated perfused hearts stained with a transmembrane voltage-sensitive dye. A computer-controlled laser beam scanned a grid of 128 recording spots on the heart every ms. The fluorescent light intensity, which changes in proportion to changes in the transmembrane potential of cells at each recording spot, was detected with a photomultiplier tube. Individual transmembrane potential recordings at each spot were then obtained by demultiplexing the fluorescence signal.

Description:

This project uses optical mapping techniques to explore how defibrillation occurs. We think that the defibrillation shock produces rapid changes in the transmembrane voltages of cells during the time that the shock is turned on, and that these changes ultimately produce defibrillation. The shock lasts only about 5 milliseconds, and so our measurements need to be fast and their times precisely controlled. We use a fast laser scanner system in which the beam is steered to spots on the heart with acousto-optic deflectors. This allows us to map the transmembrane voltage changes quickly at many spots on the heart. The effects of the shocks in hearts have proven to be very complex. The effects probably involve many factors including the shock electric field and the cellular or fiber structure of the heart. Several of the factors were predicted by mathematical models before measurements such as ours were possible. Our experiments have tested some of the predictions. The most interesting discoveries have occurred when a result did not fit a model prediction, e.g., we found "virtual electrode effects" in hearts (i.e., regions where transmembrane voltage changes were negative when they were predicted by a model to be positive). That model has been rejected. We plan to test a model called the "generalized activating function." If it is correct, this model can account for potentially all of the factors that determine the transmembrane voltage changes during a shock. This model is already known to apply to electrical stimulation of nerve fibers, but it is not known whether the model applies to defibrillation shocks in hearts. We hope to determine whether or not it applies to hearts.

Selected publications about this project:

Knisley SB, "Evidence for Roles of the Activating Function in Electric Stimulation," IEEE Transactions on Biomedical Engineering 47;1114-1119: 2000Stephen B. Knisley, Andrew E. Pollard, Vladimir G. Fast, "Effects of Electrode Myocardial Separation on Cardiac Stimulation in Conductive Solution," Journal of Cardiovascular Electrophysiology 11;1132-1143:2000.Stephen B. Knisley, Natalia Trayanova, Felipe Aguel, "Roles of Electric Field and Fiber Structure in Cardiac Electric Stimulation" Biophysical Journal 77; 1404 1417:1999

Date last updated: 1/17/2001