Mechanisms linking short- and long-term electrical remodeling in the heart .....is it a stretch?

Marrus, Scott B.; Nerbonne, Jeanne M.

doi:10.4161/chan.2.2.6104

Cited by 10 publications

(8 citation statements)

References 50 publications

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“…2, 11 In a Langendorff-perfused rabbit heart model, global alterations in strain resulted in altered expression of cardiac memory and, intriguingly, local mechanical strain sufficed to induce T wave changes similar to those of cardiac memory. 12 During RV apical pacing, myocardial strain and workload is increased in regions most distant from the site of pacing and reduced near the site of pacing.…”

Section: Introductionmentioning

confidence: 99%

Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing

Marrus

Andrews

Cooper

et al. 2012

Circ: Arrhythmia and Electrophysiology

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Background Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. This study was undertaken to produce three dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Non-invasive electrocardiographic imaging (ECGI) was used before and after one month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization resulting in a significant increase in the dispersion of repolarization. Conclusions These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous RV pacing, suggesting the novel possibility that continuous RV pacing at least partially suppresses pacemaker-induced cardiac memory.

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Section: Introductionmentioning

confidence: 99%

Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing

Marrus

Andrews

Cooper

et al. 2012

Circ: Arrhythmia and Electrophysiology

Self Cite

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“…The Q-T interval of the electrocardiogram, a measure of the delay between ventricular depolarization and repolarization, has been observed to lengthen, and the Twave to flatten, when ventricular contraction occurs rapidly against a reduced afterload, in animal tissue preparations and in the human heart [42,43]. Commonly this affect is attributed to changes in action potential duration that lead to dispersion of the repolarization gradient, though the nature of these changes is unsettled and is likely dependent on heart rate [44][45][46][47][48].…”

Section: Organ Scale: Cardiac Electromechanical Interactionsmentioning

confidence: 99%

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

Pfeiffer

Tangney

Omens

et al. 2014

Journal of Biomechanical Engineering

103

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Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation-contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation-contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.

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“…Taken together, these reports suggest that tissue stretch is a prerequisite for T-wave memory and that long-term alteration of ventricular activation causes persistent electrical remodeling via a mechano-electrical feedback mechanism (Marrus and Nerbonne, 2008). It is important to point out that in this context, VER produces persistent electrophysiological changes, such as action potential prolongation, which outlast the period of applied stretch.…”

Section: Introductionmentioning

confidence: 94%

The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart

Werdich

Brzezinski

Jeyaraj

et al. 2012

Progress in Biophysics and Molecular Biology

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Altered mechanical loading of the heart leads to hypertrophy, decompensated heart failure and fatal arrhythmias. However, the molecular mechanisms that link mechanical and electrical dysfunction remain poorly understood. Growing evidence suggest that ventricular electrical remodeling (VER) is a process that can be induced by altered mechanical stress, creating persistent electrophysiological changes that predispose the heart to life-threatening arrhythmias. While VER is clearly a physiological property of the human heart, as evidenced by “T wave memory”, it is also thought to occur in a variety of pathological states associated with altered ventricular activation such as bundle branch block, myocardial infarction, and cardiac pacing. Animal models that are currently being used for investigating stretch-induced VER have significant limitations. The zebrafish has recently emerged as an attractive animal model for studying cardiovascular disease and could overcome some of these limitations. Owing to its extensively sequenced genome, high conservation of gene function, and the comprehensive genetic resources that are available in this model, the zebrafish may provide new insights into the molecular mechanisms that drive detrimental electrical remodeling in response to stretch. Here, we have established a zebrafish model to study mechano-electrical feedback in the heart, which combines efficient genetic manipulation with high-precision stretch and high-resolution electrophysiology. In this model, only ninety minutes of ventricular stretch caused VER and recapitulated key features of VER found previously in the mammalian heart. Our data suggest that the zebrafish model is a powerful platform for investigating the molecular mechanisms underlying mechano-electrical feedback and VER in the heart.

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Mechanisms linking short- and long-term electrical remodeling in the heart .....is it a stretch?

Cited by 10 publications

References 50 publications

Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing

Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart

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