Electrical Stimulation Of Cardiac Tissue Research Articles

A Tissue Engineering Chamber for Continuous Pulsatile Electrical Stimulation of Vascularized Cardiac Tissues In Vivo.

Background: Cardiomyocytes derived from pluripotent stem cells are immature. Maturation of cardiomyocytes is a multifactorial dynamic process that involves various factors in vivo that cannot be fully recapitulated in vitro. Here, we report a novel tissue engineering chamber with an integrated electrical stimulator and electrodes that will allow wireless electrical stimulation of cardiac tissue in vivo. Materials and Methods: Immunocompromised rats were implanted with tissue engineering chambers containing the stimulator and electrodes, and control chambers (chambers with electrical stimulator but without the electrodes) in the contralateral limb. Each chamber contained cardiomyocytes derived from human induced pluripotent stem cells (iPSCs). After 7 days of chamber implantation, the electrical stimulators were activated for 4 h per day, for 21 consecutive days. Results: At 4 weeks postimplantation, cardiomyocytes derived from human iPSCs survived, were assembled into compact cardiac tissue, and were perfused and vascularized by the host neovessels. Conclusion: This proof-of-principle study demonstrates the biocompatibility of the tissue engineering chamber with integrated electrical stimulator and electrodes. This could be utilized to study the influence of continuous electrical stimulation on vascularized cardiac or other tissues in vivo.

Optical mapping of calcium distribution reveals make and break excitation modes

Background: It is known that electrical stimulation of cardiac tissue can occur by make or break mechanisms and that virtual electrode polarization underlies these phenomena. Additionally, calcium transients can play a key role in slow conduction and induction of reentry. In this study we investigated the intracellular calcium (Cai) distribution during stimulation in systolic and diastolic cardiac tissue.

Approximate analytical solutions of the Bidomain equations for electrical stimulation of cardiac tissue with curving fibers.

The mechanism by which an applied electric field stimulates cardiac tissue far from the stimulating electrodes is not wholly understood. One possible mechanism relates the curving cardiac fibers to the induced membrane currents and transmembrane potentials. However, we lack a qualitative understanding of where these areas of polarization will occur when an electric field is applied to a sheet of cardiac tissue with curving fibers. In our study, we derive an analytical model for the transmembrane potential, dependent on the gradient of the fiber angle theta, for a two-dimensional passive sheet of cardiac tissue exhibiting various fiber geometries. Unequal anisotropy ratios are crucial for our results. We compare the results from our analytical solution to a numerical calculation using the full bidomain model. The results of our comparison are qualitatively consistent, albeit numerically different. We believe that our analytical approximation provides a reliable prediction of the polarization associated with an electric field applied to cardiac tissue with any fiber geometry and a qualitative understanding of the mechanisms behind the virtual electrode polarization.

The effect of plunge electrodes during electrical stimulation of cardiac tissue.

The mechanism for far-field stimulation of cardiac tissue is not known, although many hypotheses have been suggested. This paper explores a new hypothesis: the insulated plunge electrodes used in experiments to map the extracellular potential may affect the transmembrane potential when an electric field is applied to cardiac tissue. Our calculation simulates a 10-mm-diameter sheet of passive tissue with a circular insulated plunge electrode in the middle of it, ranging in diameter from 0.05 to 2 mm. We calculate the transmembrane potential induced by a 500-V/m electric field. Our results show that a transmembrane potential is induced around the electrode in alternating areas of depolarization and hyperpolarization. If the electric field is oriented parallel to the myocardial fibers, the maximum transmembrane potential is 89 mV. A layer of fluid around the electrode increases the transmembrane potential. We conclude that plunge electrodes may introduce artifacts during experiments designed to study the response of the heart to strong electric shocks.

Search for the optimal mode of electrical stimulation of cardiac tissue

Search for the optimal mode of electrical stimulation of cardiac tissue

Electrical stimulation of cardiac tissue by a bipolar electrode in a conductive bath.

A three-dimensional (3-D) computer simulation of the electrical stimulation of passive cardiac tissue from a bipolar electrode placed within a conductive bath is presented. Through the bidomain model, the syncytial and anisotropic properties of cardiac tissue are taken into account; tissues with equal anisotropy and no transverse coupling are also considered. The membrane is represented by a capacitor and passive resistor in parallel. Located within an isotropic bath, the bipolar electrode is oriented either perpendicular or parallel to the tissue surface. For anisotropic tissue with a small cathode-tissue separation, the tissue surface is highly depolarized under the cathode with the depolarization persisting a considerable distance from the electrode in the transverse fiber direction. Adjacent to this region in the longitudinal direction, areas of hyperpolarization exist. At large distances from the cathode, the tissue surface is hyperpolarized in all directions when the electrode axis is perpendicular to the tissue. In the parallel case, surface depolarization creates buried regions of hyperpolarization. For the perpendicular configuration, the ratio of the steady-state maximum depolarization to steady-state maximum hyperpolarization, an estimate of the ratio of anodal to cathodal threshold, decreases rapidly with increasing cathode-tissue separation. In the parallel case, the depth of the conductive bath significantly affected the transmembrane potential distribution in the tissue. The use of a 3-D model more realistically simulates real-life electrical stimulation (such as stimulation with an implantable pacemaker) and provides insight into the effect of the volume conductor adjacent to the tissue.

The laws of electrical stimulation of cardiac tissue

Classic description of the criteria for cardiac stimulation is by the strength-duration curve which may be presented for current, energy, or charge. Minima for each of these occur at different waveform durations. The fundamental mechanism by which the stimulus is effective is altering the polarization potential of the cell membranes in the heart. Partial depolarization of these cells initiates a cascade leading to complete depolarization which in turn triggers cardiac cell contraction. Active propagation of the depolarization from cell to cell is the mechanism for activation of the entire heart when stimulation is used for pacemaking. For depolarization with much stronger shocks, this depolarization mechanism in some cells is combined with hyperpolarization in other cells. The hyperpolarization causes anodal block of propagation. Two methods are used to study cardiac stimulation, the threshold concept and the probability concept, and each method has advantages and limitations. Many variables affect the capability of an electrical shock to stimulate the heart to a desired response. These include the current waveform the characteristics of the electrodes used to inject the current into the tissue, the disorder being treated, the mass of cells required to be effected, metabolic variables (such as temperature or pH of the the tissue), drugs, and the geometric arrangements of electrodes and body organs. Of particular engineering interest are different effectiveness of different electrical waveforms, and the electrode characteristics of half-cell potentials, polarization potentials and materials. Equivalent circuits are presented for the complex and nonlinear, interactive behavior of the electrical shock, electrodes, and tissues.

A mathematical model of make and break electrical stimulation of cardiac tissue by a unipolar anode or cathode.

Numerical simulations of electrical stimulation of cardiac tissue using a unipolar extracellular electrode were performed. The bidomain model with unequal anisotropy ratios represented the tissue, and the Beeler-Reuter model represented the active membrane properties. Four types of excitation were considered: cathode make (CM), anode make (AM), cathode break (CB), and anode break (AB). The mechanisms of excitation were: for CM, tissue under the cathode was depolarized to threshold; for AM, tissue at a virtual cathode was depolarized to threshold; for CB, a long cathodal pulse produced a steady-state depolarization under the cathode and hyperpolarization at a virtual anode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB, a long anodal pulse produced a steady-state hyperpolarization under the anode and depolarization at a virtual cathode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB stimulation, decay of the hyperpolarization faster than that of the depolarization was necessary. The thresholds for rheobase and diastolic CM, AM, CB, and AB stimulation were 0.038, 0.41, 0.49, and 5.3 mA, respectively, for an electrode length of 1 mm and a surface area of 1.5 mm2. Threshold increased as the size of the electrode increased. The strength-duration curves for CM and AM were similar except when the duration was shorter than 0.2 ms, in which case the AM threshold rose more quickly with decreasing duration than did the CM threshold. CM and AM resulted in similar strength-frequency curves. The model agrees qualitatively, but (in some cases) not quantitatively, with experiments.

Electrical stimulation of cardiac tissue: a bidomain model with active membrane properties

Numerical calculations simulated the response of cardiac muscle to stimulation by electrical current. The bidomain model with unequal anisotropy ratios represented the tissue, and parallel leak and active sodium channels represented the membrane conductance. The speed of the wavefront was faster in the direction parallel to the myocardial fibers than in the direction perpendicular to them. However, for cathodal stimulation well above threshold, the wavefront originated farther from the cathode in the direction perpendicular to the myocardial fibers than in the direction parallel to them, consistent with observations of a dog-bone-shaped virtual cathode made by Wikswo et al., Circ. Res. 68:513-530, 1991. The model showed that the virtual cathode size and shape were dependent upon both membrane and tissue conductivities. Increasing the peak sodium conductance or reducing the transverse intracellular conductivity accentuated the dog-bone shape, while the opposite change caused the virtual cathode to become more elliptical, with the major axis of the ellipse transverse to the fiber direction. A cathodal stimulus created regions of hyperpolarization that slowed conduction of the wavefront propagating parallel to the fibers. An anodal stimulus evoked a wavefront with a complex shape; activation originated from two depolarized regions 1 to 2 mm from the stimulus site along the fiber direction. The threshold current strength (0.5 ms duration pulse) for a cathodal stimulus was 0.048 mA, and for an anodal stimulus was 0.67 mA. When the model was modified to simulate the effect of electropermeabilization, which may be present when the transmembrane potential reaches very large values near the stimulating electrode, our qualitative conclusions remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Bipolar Stimulation of Cardiac Tissue Using an Anisotropic Bidomain Model

One of the fundamental electrophysiologic problems that has not yet been completely elucidated is the response of cardiac tissue to externally applied electric currents. A limited number of theoretical and experimental techniques has been used to study the electric behavior of cardiac tissue in the presence of stimulating currents, and to demonstrate that the anisotropy in the passive electrical properties of the tissue plays an important role in the genesis and propagation of the activation wavefront and the resulting potential distributions. In this work we have applied the finite element method to study the electric and magnetic fields produced by cardiac tissue in response to bipolar current injection, using a linear bidomain model to represent the tissue. We found that the transmembrane potential distribution close to the stimulus electrode has a rather complex geometrical pattern, with adjacent hyperpolarized and depolarized regions. This behavior is consistent with previous theoretical and experimental results and may have implications in the study of electrical stimulation of cardiac tissue that are not apparent using other models.

Current injection into a two-dimensional anisotropic bidomain

A two-dimensional sheet of anisotropic cardiac tissue is represented with the bidomain model, and the finite element method is used to solve the bidomain equations. When the anisotropy ratios of the intracellular and extracellular spaces are not equal, the injection of current into the tissue induces a transmembrane potential that has a complicated spatial dependence, including adjacent regions of depolarized and hyperpolarized tissue. This behavior may have important implications for the electrical stimulation of cardiac tissue and for defibrillation.