Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart
スポンサーリンク
概要
- 論文の詳細を見る
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 heart failure, functional downregulation of K<SUP>+</SUP> currents and alterations in depolarizing Na<SUP>+</SUP> and Ca<SUP>2+</SUP> 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 heart failure with dyssynchronous LV contraction (DHF). Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF-induced downregulation of K<SUP>+</SUP> current and improved Na<SUP>+</SUP> channel gating. CRT significantly improved Ca<SUP>2+</SUP> homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviated DHF-induced prolongation of APD in the lateral wall myocytes and reduced the LV regional gradient of APD, and suppressed development of early afterdepolarizations. In conclusion, CRT partially restores the DHF-induced ion channel remodeling, abnormal Ca<SUP>2+</SUP> homeostasis, blunted β-adrenergic response 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.
著者
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KAMAKURA Shiro
National Cardiovascular Center
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AIHARA Naohiko
National Cardiovascular Center
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SHIMIZU Wataru
National Cardiovascular Center
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Okamura Hideo
National Cardiovascular Center
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Noda Takashi
National Cardiovascular Center
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Yamada Yuko
National Cardiovascular Center
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Miyamoto Koji
National Cardiovascular Center
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Satomi Kazuhiro
National Cardiovascular Center
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Kass David
Johns Hopkins University School of Medicine
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Tomaselli Gordon
Johns Hopkins University School of Medicine
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Aiba Takeshi
National Cerebral and Cardiovascular Center
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Nakajima Ikutaro
National Cerebral and Cardiovascular Center
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Tomaselli Gordon
Johns Hopkins Medical Institutions
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Kass David
Johns Hopkins Medical Institutions
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Miyamoto Koji
National Cerebral and Cardiovascular Center
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