胺碘酮对肥厚心肌钙调蛋白激酶活性的影响  

Effect of long-term oral administration of amiodarone on the activity of calmodulin kinase in rabbit with ventricular hypertrophy

作　　者：吴蔚[1] 张存泰[1] 陈柏迪[1] 贺莉[1] 任勇[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,湖北武汉430030

出　　处：《中国心脏起搏与心电生理杂志》2007年第4期342-344,共3页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然科学基金资助项目(项目编号:30470714)

摘　　要：目的观察口服胺碘酮对肥厚心肌细胞钙调蛋白激酶(CaMK)活性的影响,探讨胺碘酮抗心律失常的作用机制。方法30只家兔随机分为假手术组、心肌肥厚组和胺碘酮组,每组10只,喂养3个月,制备兔左室楔形心肌块。同步记录楔形心肌块容积心电图和内、外膜心肌细胞跨膜动作电位(TAP),程序电刺激诱发室性心律失常,并观察各组QT间期、跨室壁复极离散度(TDR)、早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的诱发率。利用放射免疫法测定心肌细胞CaMK活性。结果胺碘酮组和心肌肥厚组QT间期、内外膜心肌细胞TAP复极90%时程(APD90)和TDR均较假手术组明显延长(P<0.01),胺碘酮组QT间期和内、外膜心肌细胞APD90与心肌肥厚组相比进一步延长(P<0.05),但对TDR无明显影响。与假手术组比较,心肌肥厚组EAD和Tdp的发生率较假手术组明显升高(P<0.01),胺碘酮组EAD和Tdp的发生率较心肌肥厚组降低(P<0.05)。心肌肥厚组心肌细胞CaMK活性较假手术组明显升高,胺碘酮组CaMK活性较心肌肥厚组降低(P均<0.05)。结论胺碘酮抗心律失常的作用机制可能部分与抑制CaMK活性有关。Objective To investigate the effect of long-term oral administration of amiodarone on the activity of calmodulin kinase in rabbit with ventricular hypertrophy. Methods Ventricular hypertrophy was induced by a constriction of the abdominal aorta in rabbits. By using arterially perfused rabbit ventricular wedge preparations, transmembrane action potentials from epicardium and endocardium were simultaneously recorded together with a transmural ECG. Assay of CaM kinase activity was performed. Results Left ventricular hypertrophy（LVH） produced significant prolongation in ventricular APD50 and QT interval and a marked increase in transmural dispersion of repolarization （TDR）. Amiodarone caused a further increase in ventricular APD50 and QT interval,but not in TDR. Early afterdepolarization and torsade de pointes in LVH were suppressed by amidarone. Increased activity of calmodulin kinase in LVH was suppressed by amidarone. Conclusions The fact that amiodarone suppressed activity of calmodulin kinase may be associated with its therapeutic mechanism for antiarrhythmias.

关 键 词：心血管病学 心肌肥厚 钙调蛋白激酶 跨膜动作电位 跨室壁复极离散度 胺碘酮 

分 类 号：R972.2[医药卫生—药品]