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Remodeling of Cardiac Repolarization: Mechanisms and Implications of Memory

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Cardiac Electrophysiology Review

Abstract

Memory is a well established property of biological organisms, allowing them to adapt to theirenvironment and respond to novel stimuli. Sensitization occurs in response to a noxious stimulus, and increasesthe behavioral response to subsequent stimuli. In contrast, habituation occurs in response to an innocuousstimulus, and decreases the behavioral response to subsequent stimuli. Therefore, the response of an organismto a stimulus does not simply depend on the stimulus, but also on previous stimuli that the organism hasreceived.

Similarly, the response of the heart to a stimulus does not simply depend on the stimulus, but also onprevious patterns of depolarization and repolarization, due to electrical remodeling. Electrical remodeling,the persistent change in electrophysiological properties of myocardium in response to a change in rate oractivation sequence, has been well described in atria. It can be induced by rapid pacing or atrial fibrillation(AF), and results in shortened atrial refractory period and increased susceptibility to atrialarrhythmias. These changes have been associated with alterations of potassium and calcium currents. However,the fundamental mechanisms responsible for triggering changes in channel expression in response to alterationsin rate and activation sequence in AF are poorly understood. Even less is known about electrical remodeling inventricle. Rapid ventricular pacing or an alteration of ventricular activation sequence produces persistentchanges in heterogeneity of repolarization and, in contrast to atria, a prolongation of action potentialduration. Ventricular electrical remodeling is responsible for “T-wave memory,” which is observedcommonly in patients after periods of altered activation sequence (e.g., chronic pacing). Thesechanges have been associated with alterations of potassium currents, specifically Ito, implying thatelectrical remodeling is heterogeneously expressed in the different cell types across the transmural wall.Finally, remodeling of gap junctions may also play a prominent role in action potential changes duringremodeling. The signal transduction pathways through which a change in rate or activation sequence triggerschanges in the expression of ionic currents are being actively investigated.

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  1. The Heart and Vascular Research Center, and The Departments of Medicine and Biomedical Engineering, Case Western Reserve University, MetroHealth Campus, Cleveland, Ohio, USA

    Imad Libbus & David S. Rosenbaum

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Libbus, I., Rosenbaum, D.S. Remodeling of Cardiac Repolarization: Mechanisms and Implications of Memory. Card Electrophysiol Rev 6, 302–310 (2002). https://doi.org/10.1023/A:1016349613464

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