Stimulatory Effects of a Spatial Variation of Extracellular Conductance in an Electric Field

According to theory, spatial variations in extracellular resistance introduce transmembrane currents at borders between regions of high and low extracellular resistance due to redistribution of current between intracellular and extracellular spaces.22 For example, a decrease in extracellular resistance at a certain location along the direction of intracellular and extracellular current flow will produce a larger current extracellularly by redistribution of some of the intracellular current to the extracellular space. This redistribution produces outward transmembrane current and a positive change in transmembrane potential. Effects of some heart interfaces and alterations in extracellular conductance on the transmembrane potential have been demonstrated.7'23 Redistribution due to extracellular structures of the heart, such as a region of connective tissue or a blood vessel, might produce far-field stimulatory effects. However, that hypothesis has not been experimentally validated.

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Figure 4: Maps of change in transmembrane potential (AVm) determined from the ratio, and transmittance of the indium tin oxide (ITO) (A transmittance) determined with red fluorescence in a rabbit heart during field stimulation pulse given in action potential plateau. Top row shows AVm for each S2 polarity with ITO disc on the heart. Second row shows AVm for identical S2 after disc was removed. The third row shows the difference in AVm between the above plots, an estimate of the effect produced by the disc. The AVm and difference in AVm are expressed as a percentage of the action potential amplitude. Rows 4 and 5 show the A transmittance with and without the disc as percentages. (From Knisley and Pollard, Am J Physiol Heart Circ Physiol 289, H1137-H1146, 2005, figure 4. Reproduced with permission.)

Tests with an inactive extracellular conductor were performed to see whether such changes in transmembrane potentials occur in tissue under the conductor and correspond to the current redistribution hypothesis. These experiments used ITO as the conductor, while the shock was applied to the heart from mesh electrodes to produce an electric field in the region containing the ITO. Optical mapping was performed in the tissue under and on either side of the ITO. Figure 4 illustrates an example of results.

The maps illustrate fluorescence measurements both with an inactive ITO disc on the heart and without the disc, which serves as a control. A control is useful because there are transmembrane potential changes in the far field in hearts even when no artificial change in extracellular resistance is introduced. The difference between the map with the disc and the control represents the effect of the disc. ITO-heart interfacial current estimated from the red fluorescence signal indicates opposite interfacial currents at the left and right edges of the disc, consistent with redistribution of current between the heart and ITO. The results essentially show a cathodal stimulatory effect near the edge of the inactive disc facing the real shock anode, and an anodal stimulatory effect near the edge of the disc facing the real shock cathode.

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