Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart

Takeshi Aiba, Ikutaro Nakajima, Takashi Noda, Hideo Okamura, Yuko Yamada, Koji Miyamoto, Kazuhiro Satomi, Naohiko Aihara, Shiro Kamakura, Wataru Shimizu, David Kass, Gordon F. Tomaselli

Research output: Contribution to journalArticle

Abstract

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+ currents and alterations in depolarizing Na+ and Ca2+ 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, <-adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF-induced downregulation of K+ current and improved Na+ channel gating. CRT significantly improved Ca2+ homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted <-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 Ca2+ homeostasis, blunted <-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.

Original languageEnglish (US)
JournalJournal of Arrhythmia
Volume27
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Cardiac Resynchronization Therapy
Action Potentials
Heart Failure
Ion Channels
Adrenergic Agents
Muscle Cells
Homeostasis
Down-Regulation
Adrenergic Receptors
Cardiac Arrhythmias
Animal Models
Mortality

Keywords

  • heart failure
  • ion channels
  • resynchronization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart. / Aiba, Takeshi; Nakajima, Ikutaro; Noda, Takashi; Okamura, Hideo; Yamada, Yuko; Miyamoto, Koji; Satomi, Kazuhiro; Aihara, Naohiko; Kamakura, Shiro; Shimizu, Wataru; Kass, David; Tomaselli, Gordon F.

In: Journal of Arrhythmia, Vol. 27, 01.01.2011.

Research output: Contribution to journalArticle

Aiba, T, Nakajima, I, Noda, T, Okamura, H, Yamada, Y, Miyamoto, K, Satomi, K, Aihara, N, Kamakura, S, Shimizu, W, Kass, D & Tomaselli, GF 2011, 'Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart', Journal of Arrhythmia, vol. 27. https://doi.org/10.4020/jhrs.27.SY15_4
Aiba, Takeshi ; Nakajima, Ikutaro ; Noda, Takashi ; Okamura, Hideo ; Yamada, Yuko ; Miyamoto, Koji ; Satomi, Kazuhiro ; Aihara, Naohiko ; Kamakura, Shiro ; Shimizu, Wataru ; Kass, David ; Tomaselli, Gordon F. / Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart. In: Journal of Arrhythmia. 2011 ; Vol. 27.
@article{b31729053bad47d5a9e5da54041fc121,
title = "Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart",
abstract = "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+ currents and alterations in depolarizing Na+ and Ca2+ 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, <-adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF-induced downregulation of K+ current and improved Na+ channel gating. CRT significantly improved Ca2+ homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted <-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 Ca2+ homeostasis, blunted <-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.",
keywords = "heart failure, ion channels, resynchronization",
author = "Takeshi Aiba and Ikutaro Nakajima and Takashi Noda and Hideo Okamura and Yuko Yamada and Koji Miyamoto and Kazuhiro Satomi and Naohiko Aihara and Shiro Kamakura and Wataru Shimizu and David Kass and Tomaselli, {Gordon F.}",
year = "2011",
month = "1",
day = "1",
doi = "10.4020/jhrs.27.SY15_4",
language = "English (US)",
volume = "27",
journal = "Journal of Arrhythmia",
issn = "1880-4276",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart

AU - Aiba, Takeshi

AU - Nakajima, Ikutaro

AU - Noda, Takashi

AU - Okamura, Hideo

AU - Yamada, Yuko

AU - Miyamoto, Koji

AU - Satomi, Kazuhiro

AU - Aihara, Naohiko

AU - Kamakura, Shiro

AU - Shimizu, Wataru

AU - Kass, David

AU - Tomaselli, Gordon F.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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+ currents and alterations in depolarizing Na+ and Ca2+ 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, <-adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF-induced downregulation of K+ current and improved Na+ channel gating. CRT significantly improved Ca2+ homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted <-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 Ca2+ homeostasis, blunted <-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.

AB - 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+ currents and alterations in depolarizing Na+ and Ca2+ 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, <-adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF-induced downregulation of K+ current and improved Na+ channel gating. CRT significantly improved Ca2+ homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted <-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 Ca2+ homeostasis, blunted <-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.

KW - heart failure

KW - ion channels

KW - resynchronization

UR - http://www.scopus.com/inward/record.url?scp=85009577075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009577075&partnerID=8YFLogxK

U2 - 10.4020/jhrs.27.SY15_4

DO - 10.4020/jhrs.27.SY15_4

M3 - Article

VL - 27

JO - Journal of Arrhythmia

JF - Journal of Arrhythmia

SN - 1880-4276

ER -