Madison Stockton Spach
James B. Duke Professor Emeritus of Medicine
The aims of the research are to: 1) establish an experimental basis for cardiac propagation at a cellular level; 2) develop a quantitative representation (model) of microscopic multidimensional propagation based on natural differences in cell geometry and the distribution of the cellular connections; and, 3) explore the sensitivity of the major determinants of conduction (e.g., sodium current, maximum dV/dt) and macroscopic conduction events to variations in cellular geometry and the topology of the side-to-side connections between cells. The most common cause of tachyarrhythmias in patients is some form of reentry. Our results indicate that changes in the distribution of the gap junctions, previously considered of minor importance, create new microscopic structural mechanisms that cause reentry. Consequently, the research is designed to
study the interrelationships between cell-to-cell current flow, ionic current flow through cell membranes, the extracellular potential field, and propagation phenomena. Experimentally, transmembrane potentials and extracellular potentials are measured with high temporal and spatial resolution at a microscopic level. The effects of normal and altered initial conditions of the ion
channel currents are being evaluated, and multidimensional cellular models of propagation are being developed. Such models are essential since they provide the linear passive properties at a cellular level that are necessary to link the ion channel currents to the macroscopic propagation events. The major focus is on exploring the sensitivity of macroscopic propagation events to changes in cell geometry and the loss of side-to-side electrical connections between fibers that
occur during development and aging.
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