© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts
aDepartment of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
bDepartment of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, and Department of Veterans Affairs Medical Center, Oklahoma City, USA
cLaboratory of Experimental Cardiology, University of Leuven, Leuven, Belgium
* Corresponding author. Tel.: +31-43-3875093; fax: +31-43-3875104 p.volders@cardio.azm.nl
Received 14 July 1999; accepted 25 January 2000
KEYWORDS Arrhythmia (mechanisms); Calcium (cellular); Long QT syndrome; Membrane potential; Impulse formation; SR (function)
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1 Introduction |
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Afterdepolarizations are oscillations of the transmembrane potential that depend on the preceding action potential (AP) for their generation and can give rise to new APs when they reach a critical threshold for activation of a depolarizing current. This form of abnormal impulse generation is called ‘triggered activity’ [1].
Two types of afterdepolarizations have been distinguished: delayed (DADs) and early afterdepolarizations (EADs). DADs have been defined as "oscillations in membrane potential that occur after repolarization of an action potential" [2]. EADs are generated during the AP and have been defined as "oscillations at the plateau level of membrane potential or later during phase 3 of repolarization" [2]. Depending on the level of the membrane potential at which they are generated, EADs can trigger new APs that may appear as ectopic beats on the ECG. EADs can also augment electrical heterogeneity in regions of neighboring myocardium, which can lead
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2 Cellular mechanisms of Ca2+ homeostasis and their relation to EADs |
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2.1 Ca2+ homeostasis in normal cardiac cells
2.2 Differences of [Ca2+] between the bulk cytoplasm and the subsarcolemmal space
2.3 Spontaneous Ca2+ release from the SR and mechanisms of DADs
2.4 Ionic mechanisms of EADs
2.4.1 Role of window INa and ICaL
2.4.2 Evidence for [Ca2+]cyt-dependent mechanisms of EADs
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3 EADs and arrhythmogenesis in multicellular preparations and the intact animal heart |
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3.1 EADs in multicellular preparations: consequences for arrhythmogenesis
3.2 Simultaneous appearance of EADs and DADs in the intact heart
3.3 EADs occurring in conditions associated with myocardial Ca2+ overload
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4 Clinical relevance of EADs in the congenital and acquired long-QT syndromes |
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4.1 Congenital long-QT syndromes
4.2 Acquired long-QT syndromes
4.3 Cardiac hypertrophy and failure
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5 Time to revise current concepts on EADs |
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