The Effect Of The L-CA～(2+) Channel Blockers On Inositol 1, 4, 5 Trisphosphate Receptor Expression In Atrial Tissue In Patients With Chronic Atrial Fibrillation

OBJECTIVES: We examined whether patients with chronic atrial fibrillation, who were treated with L-Ca2+ Channel Blockers, have different IP3 receptors expression compared with those who didn't use L_ Ca2+ Channel Blockers.BACKGROUND: The phenomena of cytosolic Ca2+ overload has been thought to be the major mechanism initiating and maintaining atrial fibrillation. It has been reported that verapamil can block the electrical remodeling. Now we know that IP3 receptor is the very important Ca2+ regulatory protein in atrial tissue and the previous study had proved its up-regulation in atrial tissue in patients with chronic atrial fibrillation. Inthe study of the treatment of paroxysmal atrial fibrillation, Diltiazem is found to reduce episodes of atrial fibrillation and Perindopril + Diltiazem is found to slow down the speed of left atrial enlargement.METHODS: We analyzed IP3 receptor expression in the right atrial myocardium from 12 patients with congenital cardiovascular diseases as the control group, 8 patients with mitral valvular diseases with normal sinus rhythm as the NSR group and 17 patients with mitral valvular diseases with AF, among whom there are 8 ones had been treated with Diltiazem for more than 3 months as the AF/D+ group, but the others had never used Diltiazem in their treatment as the AF/D- group. Echocardiographic data and electrocardiogram of all the patients were obtained preoperatively.RESULTS: 1). The relative expression levels of IP3 receptor protein were significantly greater in AF/D- (0.67+0.30) and AF/D+ (0.51+0.22) than it was in NSR (0.36+0.20; p<0.05), and all were significantly greater than that in control group (0.18+0.10; p<0.01). 2). The relative expression levels of IP3 receptor messenger RNA was significantly greater in the AF/D+ (0.024+0.007) , AF/D- (0.026+0.008) and NSR (0.021+0.005) than it was in the control group (0.010+0.005, p<0.05), but there were no significant difference in the three group of AF/D+, AF/D- and NSR. 3 ) . The relative expression level of IP3 receptor expression protein wassignificantly greater in AF/D- than it was in AF/D+ (p<0.05), but the relative expression levels of IP3 receptor expression messenger RNA in these two groups didn't significantly differ (p>0.05). 4). The left atrial dimension obtained by echocardiographic examination preoperatively in AF/D- was greater than it was in AF/D+, but not significantly (p>0.05). 5). The expression level of IP3 receptor was significantly higher in the patients with VR > 100bpm than in the patients with VR<100bpm.CONCLUSIONS: In chronic atrial fibrillation patients, there is up-regulation of IP3 receptor expression, which is important in regulating intracellular Ca2+ homeostasis. L- Ca2+ channel blockers can reduce IP3 receptor expression in chronic atrial fibrillation, which may be meaningful in the treatment of chronic atrial fibrillation.