Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation

被引:96
作者
Ohkusa, T
Ueyama, T
Yamada, J
Yano, M
Fujumura, K
Esato, K
Matsuzaki, M
机构
[1] Yamaguchi Univ, Sch Med, Dept Internal Med 2, Yamaguchi 7558505, Japan
[2] Yamaguchi Univ, Sch Med, Dept Surg 1, Yamaguchi 7558505, Japan
关键词
D O I
10.1016/S0735-1097(99)00169-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVES Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca(2+) regulator proteins in the atrial myocardium. BACKGROUND Clinically, AF is the most frequently encountered arrhythmia. Resent studies indicate that an inability to maintain intracellular Ca(2+) homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Cazf abnormalities are an important mediator of sustained AF. METHODS We measured the maximum number of [(3)H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca(2+)-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS In AF patients, 1) Bmax was significantly lower in each atrium (0.21 +/- 0.03 pmol/mg [right], 0.16 +/- 0.03 pmol/mg [left]) than in the right atrium (0.26 +/- 0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2) +/- 1.28 x 10(-2)) and right (1.70 x 10(-2) +/- 1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2) +/- 2.79 x 10(-2)); and 5) the expression level of Ca(2+) ATPase mRNA was significantly lower in both the left (5.67 x 10(-2) +/- 4.01 x 10(-2)) and right (7.71 x 10(-2) +/- 3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2) +/- 3.92 x 10(-2)) of NSR patients. CONCLUSIONS These results provide the first direct evidence of abnormalities in the Ca(2-) regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF. (C) 1999 by the American College of Cardiology.
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页码:255 / 263
页数:9
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