Rate-dependent force, intracellular calcium, and action potential voltage alternans are modulated by sarcomere length and heart failure induced-remodeling of thin filament regulation in human heart failure: A myocyte modeling study

Progress in Biophysics and Molecular Biology
Melanie A Zile, Natalia A Trayanova

Abstract

Microvolt T-wave alternans (MTWA) testing identifies heart failure patients at risk for lethal ventricular arrhythmias at near-resting heart rates (<110 beats per minute). Since pressure alternans occurs simultaneously with MTWA and has a higher signal to noise ratio, it may be a better predictor of arrhythmia, although the mechanism remains unknown. Therefore, we investigated the relationship between force alternans (FORCE-ALT), the cellular manifestation of pressure alternans, and action potential voltage alternans (APV-ALT), the cellular driver of MTWA. Our goal was to uncover the mechanisms linking APV-ALT and FORCE-ALT in failing human myocytes and to investigate how the link between those alternans was affected by pacing rate and by physiological conditions such as sarcomere length and heart failure induced-remodeling of mechanical parameters. To achieve this, a mechanically-based, strongly coupled human electromechanical myocyte model was constructed. Reducing the sarcoplasmic reticulum calcium uptake current (Iup) to 27% was incorporated to simulate abnormal calcium handling in human heart failure. Mechanical remodeling was incorporated to simulate altered thin filament activation and crossbridge (XB) cycling rates. A d...Continue Reading

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Citations

Jan 19, 2016·Progress in Biophysics and Molecular Biology·T Alexander Quinn, Crystal M Ripplinger
Dec 30, 2015·Progress in Biophysics and Molecular Biology·Colin H PetersPeter C Ruben
Jun 27, 2017·Progress in Biophysics and Molecular Biology·Melanie A Zile, Natalia A Trayanova
Aug 25, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Melanie A Zile, Natalia A Trayanova
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Aug 1, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Aurore LyonJoost Lumens

Related Concepts

Nerve Impulses
Kinematics
Calcium
Myocardial Failure
Sarcomeres
Alanine Transaminase
Calcium
Heart Failure
Ventricular Arrhythmia
Intracellular

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