Alterations in cardiac sarcoplasmic reticulum Ca(2+) regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation

作者：Ohkusa T^*; Ueyama T; Yamada J; Yano M; Fujumura K; Esato K; Matsuzaki M

来源：Journal of the American College of Cardiology, 1999, 34(1): 255-263.

DOI：10.1016/S0735-1097(99)00169-2

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.

• 出版日期1999-7