Electrical stimulation of cardiac tissue is crucial for pacing and defibrillation of the heart. Yet, the fundamental mechanisms governing how electric fields polarize cardiac tissue are poorly understood. The goal of this proposal is to study the mechanism of excitation and reentry induction during electrical stimulation of the heart. There are 7 specific aims, each stated as a hypothesis. 1) Plunge electrodes influence the electrical behavior of the tissue during a strong shock. Arrays of plunge electrodes are often used to record the extracellular potential. Each plunge electrode represents a resistive inhomogeneity which may polarize the tissue during a defibrillation shock. Thus, plunge electrodes may provide a mechanism for far-field stimulation. 2) Epicardial electrodes influence the electrical behavior of the tissue during a strong shock. Far from an electrode, current distributes between the intra- and extracellular spaces according to their respective conductivities. However, near an epicardial electrode, current leaves the intracellular space to take advantage of the low resistance extracellular path (the high conductivity electrode material), thereby depolarizing the tissue. The tissue hyperpolarizes where current reenters the tissue and redistributes back into the intracellular space. 3) Optical mapping records signals representing the transmembrane potential averaged over depth, which affects the comparison of simulations with experiments. 4) Virtual electrodes at the tissue surface induce reentry. A weak S1 stimulus through an electrode in a bath perfusing the tissue induces an outwardly propagating wave front. If a strong anodal S2 stimulus is then applied through the same electrode, it hyperpolarizes the tissue surface but depolarizes regions below the surface. These adjacent de- and hyperpolarized regions may lead to break excitation and reentry having vortex filaments below the tissue surface. 5) An S3 stimulus exerts a protective effect by terminating reentry. The S2-S3 interval determines if reentry continues or terminates by the collision of the S2 and S3 wave fronts. 6) Rapid pacing induces quatrefoil reentry. In general, unipolar pacing cannot induce reentry because there is no preferred direction for propagation failure. However, unequal anisotropy ratios provides such a prefered direction, facilitating reentry. Burst pacing should therefore induce quatrefoil reentry without strong shocks. 7) Rapid propagation through virtual anodes results in an upper level of vulnerability. Reentry is not induced if a shock is too strong. Stronger stimuli produce stronger hyperpolarization at virtual anodes. Break wave fronts propagate rapidly through this very excitable tissue, and then fail at the edge of the virtual anode, where the wave front meets refractory tissue. Computer simulations based on the bidomain model will be used to achieve these specific aims and to test these hypotheses. Each hypothesis is motivated by experimental data, and the goal of the theoretical simulations is to interpret these data.
| Mazeh, Nachaat; Roth, Bradley J (2009) A mechanism for the upper limit of vulnerability. Heart Rhythm 6:361-7 |
| Woods, Marcella C; Sidorov, Veniamin Y; Holcomb, Mark R et al. (2006) Virtual electrode effects around an artificial heterogeneity during field stimulation of cardiac tissue. Heart Rhythm 3:751-2 |
| Roth, Bradley J (2006) How to explain why ""unequal anisotropy ratios"" is important using pictures but no mathematics. Conf Proc IEEE Eng Med Biol Soc 1:580-3 |
| Beaudoin, Deborah Langrill; Roth, Bradley J (2006) The effect of the fiber curvature gradient on break excitation in cardiac tissue. Pacing Clin Electrophysiol 29:496-501 |
| Roth, Bradley J; Patel, Salil G; Murdick, Ryan A (2006) The effect of the cut surface during electrical stimulation of a cardiac wedge preparation. IEEE Trans Biomed Eng 53:1187-90 |
| Beaudoin, Deborah Langrill; Roth, Bradley J (2005) How the spatial frequency of polarization influences the induction of reentry in cardiac tissue. J Cardiovasc Electrophysiol 16:748-52 |
| Patel, Salil G; Roth, Bradley J (2005) Approximate solution to the bidomain equations for defibrillation problems. Phys Rev E Stat Nonlin Soft Matter Phys 71:021908 |
| Poelzing, Steven; Roth, Bradley J; Rosenbaum, David S (2005) Optical measurements reveal nature of intercellular coupling across ventricular wall. Am J Physiol Heart Circ Physiol 289:H1428-35 |
| Patel, Salil G; Roth, Bradley J (2005) Approximate solution to the bidomain equations for electrocardiogram problems. Phys Rev E Stat Nonlin Soft Matter Phys 72:051931 |
| Beaudoin, Deborah Langrill; Roth, Bradley J (2004) Effect of plunge electrodes in active cardiac tissue with curving fibers. Heart Rhythm 1:476-81 |
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