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A comparative modeling study of the dose dependent effects of antiarrhythmics on a cardiac cell
Tuladhar, Binaya,author.
Tuladhar, Binaya,author.
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2019
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Sudden cardiac death (SCD) in humans due to cardiac arrhythmia is one of the leading causes of mortality in the world. Antiarrhythmic drugs were developed to treat abnormal heart rhythms resulting from the irregular electrical activity of the heart. Several different classes of antiarrhythmic drugs, each primarily blocking a different ion channel, are currently available. It is essential to understand how these drugs affect the electrophysiological properties of cardiac cells. The main goal of our study is to understand how these drugs change the behavior of the ionic currents during the action potential at slower and faster heart rates in the ventricular cells of two different species. In this paper, we use mathematical models of a human ventricular cell, the Bernus model and a canine ventricular cell, the Fox model, to study the response to three different classes of antiarrhythmic drugs: Na+ channel blockers, K+ channel blockers and Ca2+ channel blockers. We compare the dose dependence of action potential duration (APD), rate dependence, hysteresis, restitution and the appearance of arrhythmias for the three classes of drugs. The Bernus model and the Fox model both predict that Na+ channel blockers will have little effect on any electrophysiologic features except at high doses; K+ channel blockers increase the APD, exhibit reverse rate-dependence and have a biphasic effect on the occurrence of arrhythmias as dose increases; and Ca2+ channel blockers decrease APD, show reverse rate-dependence and decrease the occurrence of arrhythmias. The techniques developed in this study provide a method for examining predictions of antiarrhythmic effects using more complex cardiac models.
Electric restitution plays an important role in the function of the heart and is believed to determine the stability of heart rhythms. We investigate the effects of various antiarrhythmic drugs on restitution properties of APD of human and canine ventricular cells. Both dynamic and S1-S2 restitution protocol is implemented to study the slope of the restitution curves. Our study examines the maximum slope of these curves for three classes of antiarrhythmic drugs.
Electric restitution plays an important role in the function of the heart and is believed to determine the stability of heart rhythms. We investigate the effects of various antiarrhythmic drugs on restitution properties of APD of human and canine ventricular cells. Both dynamic and S1-S2 restitution protocol is implemented to study the slope of the restitution curves. Our study examines the maximum slope of these curves for three classes of antiarrhythmic drugs.
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1 online resource (xi, 151 pages) :
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Physics and Astronomy