期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 58, 期 20, 页码 2106-2115出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2011.07.039
关键词
atrial fibrillation; atrial myocyte culture; optical mapping; repolarization alternans
资金
- National Taiwan University Hospital [98N1165, 98P24, 99S1283]
- National Science Council [96-2314-B-002-187-MY3, 98-2314-B-002-134-MY3]
- New Century Health Care Promotion Foundation
Objectives The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer. Background How rapid firings or premature beats trigger AF is not completely understood. Discordant repolarization alternans, characterized by simultaneous prolongation and shortening of APD in different myocardial regions, is central to the genesis of ventricular fibrillation. We hypothesized that repolarization alternans also is central to the initiation of multiple re-entry circuits and AF. Methods Confluent HL-1 atrial myocyte monolayer with spontaneous depolarization was cultured in silicone membrane and subjected to mechanical stretch. Rapid field pacing was used to induce alternans. A high-resolution dual optical mapping system was used to record action potentials and calcium transients. Results High-rate pacing induced APD-ALT and calcium transient in atrial myocyte monolayer. Mechanical stretch significantly decreased the thresholds for APD-ALT and calcium transient. Mechanical stretch decreased the expression of sarcoplasmic reticulum adenosine triphosphatase 2, and thus slower calcium reuptake kinetics, which was responsible for the susceptibility to alternans. Mechanical stretch did not alter the APD restitution kinetics. Mechanical stretch also enhanced spatially discordant alternans. Overexpression of sarcoplasmic reticulum adenosine triphosphatase 2 reversed all the effects of stretch on susceptibility to alternans. In intact atrium, mechanical stretch also enhanced discordant alternans. Conclusions Mechanical stretch increased the susceptibility to alternans in atrial myocytes, which may explain the susceptibility to AF in conditions of atrial stretch, such as mitral valvular heart disease, heart failure, and hypertension. (J Am Coll Cardiol 2011;58:2106-15) (C) 2011 by the American College of Cardiology Foundation
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