Electrical remodeling in the failing heart.
Electrical remodeling in the failing heart.
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DOI：
10.1097/hco.0b013e328333d3d6
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发表时间：
2010-01
影响因子：
2.3
通讯作者：
Tomaselli GF
中科院分区：
文献类型：
--
作者：
Aiba T;Tomaselli GF
We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in the heart failure with dyssynchronous LV contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure (HF) model. The electrophysiological hallmark of cells and tissues isolated from failing hearts is prolongation of action potential duration (APD) and conduction slowing. In human studies and a number of animal models of HF, functional downregulation of K currents and alterations in depolarizing Na and Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogenous particularly in the DHF. Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in HF. CRT partially reversed the DHF-induced downregulation of K current and improved Na channel gating. CRT significantly improved Ca homeostasis especially in lateral myocytes, and restored the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviated DHF-induced prolongation of APD in the lateral myocytes and reduced the LV regional gradient of APD, and suppressed development of EADs. CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted β-adrenergic responsiveness and regional heterogeneity of APD, thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improve mechanical performance of the heart.
