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GW24-e0582 The role and mechanism of late sodium current in the development of electromechanical alternans and arrhythmia in heart failure
  1. Quan Xiao-Qing,
  2. Zhang Cun-Tai
  1. Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Abstract

Objectives Heart failure is associated with electromechanical alternans that often heralds the development of malignant arrhythmias and sudden death, but the exact mechanism is unclear. Our previous studies have shown that heart failure results in an increase in late sodium current. Ranolazine (a late sodium current blocker) abolishes early after depolarisation, electromechanical alternans and arrhythmias in heart failure. The purpose of this study was to further clarity the electrophysiological and molecular mechanism of electromechanical alternans and arrhythmia in heart failure.

Methods The renovascular hypertension model was used to induce heart failure in rabbits. Transmembrane action potentials were simultaneously recorded from endocardium and epicardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedges. Spontaneous intracellular calcium elevations were measured by laser scanning confocal microscope in single cardiac myocyte.

Results At a basic cycle length of 250 ms, delayed after depolarization (DAD), electromechanical alternans and arrhythmias increased sharply in the heart failure group (P < 0.05 for both). Interestingly, compared with the heart failure group, ranolazine prevented DAD, electromechanical alternans and arrhythmias (P < 0.05 for both). In single cardiac myocyte, ranolazine abolished spontaneous intracellular calcium elevations and DAD in heart failure.

Conclusions Increase of late sodium current could influence calcium homeostasis, and then cause afterdepolarisation, electromechanical alternans and arrhythmias in heart failure. This study may provide a novel approach to prevent and treat arrhythmias in the setting of heart failure.

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