Spatial Changes in the Transmembrane Potential During Extracellular Electric Stimulation

Abstract

Abstract-The purpose of this study was to determine the spatial changes in the transmembrane potential caused by extracellular electric field stimulation. The transmembrane potential was recorded in 10 guinea pig papillary muscles in a tissue bath using a double-barrel microelectrode. After 20 S1 stimuli, a 10-ms square wave S2 shock field with a 30-ms S1-S2 coupling interval was given via patch shock electrodes 1 cm on either side of the tissue during the action potential plateau. Two shock strengths (2.1Ϯ0.2 and 6.5Ϯ0.6 V/cm) were tested with both shock polarities. In the macroscopic group, the portion of the tissue toward the anode was hyperpolarized, whereas the portion toward the cathode was depolarized, with 1 zero-potential crossing from hyperpolarization to depolarization present near the center of the tissue. In the microscopic group, only 1 zero-potential crossing was observed in the center region of the tissue, whereas, away from the center, only hyperpolarization was observed toward the anode and depolarization toward the cathode. Although these results are consistent with predictions from field stimulation of continuous representations of myocardial structure, ie, the bidomain and cable equation models, they are not consistent with the prediction of depolarization-hyperpolarization oscillation from representations based on cellular-level resistive discontinuities associated with gap junctions, ie, the sawtooth model. (Circ Res. 1998;83:1003-1014.)Key Words: hyperpolarization Ⅲ defibrillation Ⅲ simulation T o understand the mechanism of ventricular defibrillation, it is important to acquire knowledge of the transmembrane potential changes (⌬V m ) caused by the shock in addition to the action potential changes after the shock. This is because the cellular excitation and alteration in action potentials that occur after a defibrillation shock are thought to result from the changes in the transmembrane potential caused by the shock. 1,2 Several studies have been performed to obtain such information. Some studies used optical recording techniques to evaluate the ⌬V m caused by the shock field in either isolated myocytes 1,3-5 or perfused hearts. 2,6 -10 With a few exceptions, 1,3-5,11 the optical recording represents the weighted average of the ⌬V m changes in many cells. 2,7,9 Recordings of the transmembrane potential by a doublebarrel microelectrode can supply information about the ⌬V m caused by the shock from an individual cell within the myocardial syncytium. 12,13 A range of modeling studies completed over the past 15 years suggests that shock-induced ⌬V m can change markedly over the length of an individual cell.14 -17 These studies are based on the hypothesis that highly resistive gap junctions located at the cell ends create a sawtooth pattern of depolarization-hyperpolarization oscillation in the spatial distributions of V m . Experimentally, the sawtooth pattern has been observed during shocks applied to isolated myocytes, 1 with the cell end closest to the cathode depolarized and the end close...

The effect of spatial scale of resistive inhomogeneity on defibrillation of cardiac tissue

“…The effect of small scale resistive inhomogeneity due to gap junctions is clearly seen in single isolated cells, but less so in coupled pairs of cells (Sharma and Tung 2001). In intact tissue, sawtooth potentials of the amplitude required of this theory have not been seen (Zhou et al 1998).…”

“…Because the largest contribution to small scale inhomogeneities was thought to be gap junctional resistance, and because gap junctional resistance should lead to "sawtooth" profiles of transmembrane potential, this hypothesis is sometimes referred to as the sawtooth hypothesis (Krassowska et al 1987;Krassowska et al 1990). At present, the sawtooth hypothesis is not accepted by many workers in the field, largely because of experimental data suggesting that the amplitude of the sawtooth is too small to be the source of defibrillating stimuli (Gillis et al 1996;Zhou et al 1998). However, a new proposal that deserves consideration is that interlaminal clefts provide an adequate small scale resistive inhomogeneity (Hooks et al 2002).…”

The Biphasic Mystery: Why a Biphasic Shock is More Effective than a Monophasic Shock for Defibrillation

“…This is because the functions = G and = C , which give a measure of small scale resistive inhomogeneities, are not known. In fact, to date, attempts to directly observe the &&sawtooth'' potential have failed (Gillis et al, 1996;Zhou et al, 1998) leading some investigators to dispute the validity of this model. It should be noted, however, that there is no doubt that resistive inhomogeneities play an important role in the distribution of transmembrane currents during a stimulus (Fishler, 1998;Fishler & Vepa, 1998;White et al, 1998), nor can one dispute the existence of small-scale resistive inhomogeneities, only whether or not the e!ect of THE BIPHASIC MYSTERY 15 FIG.…”

Diastolic Field Stimulation: the Role of Shock Duration in Epicardial Activation and Propagation

“…Plonsey and Barr (1) hypothesized that intercellular resistance at gap junctions causes depolarization and hyperpolarization on opposite ends of each myocyte. However, attempts to experimentally verify the sawtooth effect in intact cardiac tissue have failed (2,3). Theoretical simulations using the bidomain model of cardiac tissue predict that fiber curvature and unequal anisotropy ratios between the intra-and extracellular spaces cause depolarization and hyperpolarization throughout the heart (4-7), whereas the transmural fiber rotation modulates the polarization gradient through the bulk of tissue (5).…”