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Restitution curves and the stability of reentry in three-dimensional simulations of cardiac tissue

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Computing and Visualization in Science

Abstract

Recent studies have shown that cardiac antiarrhythmic drugs may actually increase mortality in certain instances. Due to the failure of the premise that an increased refractory period alone is sufficient to provide protection, it has been posited that the slope of the action potential duration (APD) restitution curve is a critical factor in the deterioration of tachycardia into fibrillation suggesting another avenue to explore in developing new antiarrhythmic drugs. This paper examines the relationship between APD restitution curves and the breakdown of stable reentry into fibrillation in a three dimensional model of a slab of cardiac tissue. The Luo–Rudy I model was used to describe the ionic current. Three different methods were used to measure the restitution curve: the standard protocol, the dynamic protocol and that measured directly, the natural restitution curve. The effects of altering conductances and time constants controlling the individual ionic currents on restitution and breakdown were determined. Manouevres which decreased action potential duration decreased the slope of the restitution curve. Consequently, reducing the slope of the restitution curve led to scroll waves which were more stable, taking longer time to break up. The restitution curves as measured by each of the different methods differed from each other as did restitution curves computed from two-dimensional sheets of tissue. Restitution curves produced by the standard and dynamic protocols defined an envelope in which the natural restitution curve was found to lie. From single cell experiments one could not determine whether the activity would break up by examining the peak slope of the restitution curve or the region of the slope above one, although the latter tended to correlate better with the simulated activity. This result suggests that the medium plays an important role in determining what behaviour gets expressed. Finally, the best route for preventing the breakdown of tachycardia into fibrillation would be to increase the kinetics of the slow inward current since it decreases the APD the least.

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Received: 13 August 2001

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Vigmond, E.J., Leon, L.J. Restitution curves and the stability of reentry in three-dimensional simulations of cardiac tissue. Comput Visual Sci 4, 237–247 (2002). https://doi.org/10.1007/s00791-002-0080-x

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  • DOI: https://doi.org/10.1007/s00791-002-0080-x

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