Abstract
Purpose of Review: We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in heart failure with dyssynchronous left ventricular contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure model. Recent Findings: 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 Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and extracellular matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogeneous, particularly in the DHF. Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in heart failure. CRT partially reverses the DHF-induced downregulation of K current and improves Na channel gating. CRT significantly improves Ca homeostasis, especially in lateral myocytes, and restores the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviates DHF-induced prolongation of APD in the lateral myocytes, reduces the left ventricular regional gradient of APD and suppresses development of early afterdepolarizations. Summary: CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted β-adrenergic responsiveness, and regional heterogeneity of APD, and thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improving mechanical performance of the heart.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 29-36 |
| Number of pages | 8 |
| Journal | Current Opinion in Cardiology |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2010 |
| Externally published | Yes |
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Keywords
- Action potential
- Gene expression
- Heart failure
- Ion channels
- Remodeling
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Electrical remodeling in the failing heart. / Aiba, Takeshi; Tomaselli, Gordon F.
In: Current Opinion in Cardiology, Vol. 25, No. 1, 01.01.2010, p. 29-36.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Electrical remodeling in the failing heart
AU - Aiba, Takeshi
AU - Tomaselli, Gordon F.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Purpose of Review: We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in heart failure with dyssynchronous left ventricular contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure model. Recent Findings: 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 Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and extracellular matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogeneous, particularly in the DHF. Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in heart failure. CRT partially reverses the DHF-induced downregulation of K current and improves Na channel gating. CRT significantly improves Ca homeostasis, especially in lateral myocytes, and restores the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviates DHF-induced prolongation of APD in the lateral myocytes, reduces the left ventricular regional gradient of APD and suppresses development of early afterdepolarizations. Summary: CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted β-adrenergic responsiveness, and regional heterogeneity of APD, and thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improving mechanical performance of the heart.
AB - Purpose of Review: We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in heart failure with dyssynchronous left ventricular contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure model. Recent Findings: 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 Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and extracellular matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogeneous, particularly in the DHF. Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in heart failure. CRT partially reverses the DHF-induced downregulation of K current and improves Na channel gating. CRT significantly improves Ca homeostasis, especially in lateral myocytes, and restores the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviates DHF-induced prolongation of APD in the lateral myocytes, reduces the left ventricular regional gradient of APD and suppresses development of early afterdepolarizations. Summary: CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted β-adrenergic responsiveness, and regional heterogeneity of APD, and thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improving mechanical performance of the heart.
KW - Action potential
KW - Gene expression
KW - Heart failure
KW - Ion channels
KW - Remodeling
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UR - http://www.scopus.com/inward/citedby.url?scp=74249097206&partnerID=8YFLogxK
U2 - 10.1097/HCO.0b013e328333d3d6
DO - 10.1097/HCO.0b013e328333d3d6
M3 - Review article
VL - 25
SP - 29
EP - 36
JO - Current Opinion in Cardiology
JF - Current Opinion in Cardiology
SN - 0268-4705
IS - 1
ER -