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Genesis of phase 3 early afterdepolarizations and triggered activity in acquired long-QT syndrome

Authors
 Seongwook Han ; Tetsuji Shinohara ; Boyoung Joung ; Su-Kiat Chua ; Yuanfang Xie ; Shien-Fong Lin ; Mitsunori Maruyama ; Peng-Sheng Chen ; James N. Weiss ; Zhilin Qu ; Mark J. Shen 
Citation
 Circulation-Arrhythmia and Electrophysiology, Vol.4(1) : 103~111, 2011 
Journal Title
 Circulation-Arrhythmia and Electrophysiology 
ISSN
 1941-3149 
Issue Date
2011
Abstract
BACKGROUND: Both phase 2 and phase 3 early afterdepolarizations (EADs) occur in long-QT syndromes, but their respective roles in generating arrhythmias in intact cardiac tissue are incompletely understood. METHODS AND RESULTS: Intracellular Ca (Ca(i)) and membrane voltage (V(m)) were optically mapped in a quasi 2-dimensional model of cryoablated Langendorff-perfused rabbit ventricles (n=16). E-4031 (an I(Kr) blocker) combined with reduced extracellular K ([K(+)](o)) and Mg ([Mg(2+)](o)) prolonged action potential duration heterogeneously and induced phase 2 and phase 3 EADs. Whereas phase 2 EADs were Ca(i)-dependent, phase 3 EADs were not. The origins of 47 triggered activity episodes were attributed to phase 2 EADs in 12 episodes (26%) and phase 3 EADs in 35 episodes (74%). When phase 2 EADs accompanied phase 3 EADs, they accentuated action potential duration heterogeneity, creating a large V(m) gradient across the boundary between long and short action potential duration regions from which triggered activity emerged. The amplitude of phase 3 EADs correlated with the V(m) gradient (r=0.898, P<0.001). Computer simulation studies showed that coupling of cells with heterogeneous repolarization could extrinsically generate phase 3 EADs via electrotonic current flow. Alternatively, reduced I(K1) caused by low [K(+)](o) could generate intrinsic phase 3 EADs capable of inducing triggered activity at the boundary zone. CONCLUSIONS: Phase 3 EADs can be extrinsic as the result of electrotonic current across steep repolarization gradients or intrinsic as the result of low I(K1) and do not require spontaneous sarcoplasmic reticulum Ca release. Reduction of I(K1) by low [K(+)](o) strongly promotes ventricular arrhythmias mediated by phase 3 EADs in acquired long-QT syndrome caused by I(Kr) blockade.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/92990
DOI
10.1161/CIRCEP.110.959064
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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