阿托伐他汀对快速起搏兔房颤模型心房电重构的影响

Effect of atorvastatin applied to atrial tachypacing rabbits on electrical remodeling

目的:观察阿托伐他汀(ATO)对快速起搏兔房颤模型心房电重构、心房肌离子通道蛋白及心脏功能的影响,探讨阿托伐他汀防治心房颤动的电生理机制。方法:30只新西兰大白兔开胸植入心房起搏和测试电极,采用特制动物心脏起搏器快速起搏心房的方法建立兔房颤模型,将其分为对照组、起搏组和药物组。药物组预先给予阿托伐汀钙片2 mg·kg^(-1)·d^(-1)灌胃7 d,起搏组和药物组快速起搏心房48 h,期间药物组持续给药处理,分别于0 h、8 h、16 h、24 h、32 h、40 h、48 h测量心房有效不应期,计算心房频率适应性,观察心脏大小及心功能的变化,比较各组心房肌细胞离子通道蛋白Ca Lα1和Kv4.3的表达差异。结果:与对照组相比,药物组和起搏组心房有效不应期缩短,频率适应性下降,心房肌细胞离子通道蛋白Ca Lα1及Kv4.3表达水平降低(P<0.05),其中以起搏组变化最为明显。快速起搏心房48 h后,起搏组和药物组左房较对照组增大(P<0.05),而左心室大小及射血分数起搏前后均无明显差异。结论:短期快速心房起搏可引起心房有效不应期缩短,导致心房频率适应性不良,阿托伐他汀预处理可有效改善快速起搏诱导的兔心房电重构,而对心脏结构影响不大。进一步研究发现阿托伐他汀可在一定程度上抑制心房肌钾、钙离子通道蛋白水平降低,这可能是其改善电重构的机制之一。

AIM： To investigate the effect of atorvastatin（ ATO） on electrical remodeling,atrial ion channel protein expression and cardiac function in atrial tachypacing rabbits,and to explore the potential electrical mechanism of ATO in the prevention of atrial fibrillation. METHODS： The rabbits were subjected to atrial tachypacing at 600 min^（- 1）in the absence or presence of treatment with atorvastatin（ ATP and ATO groups） for 48 h,and the other 10 as sham group without pacing（ NP group）. The tachypacing model was performed by attaching pacing and testing electrodes to left atrial and connecting with custom animal cardiac pacemaker in the open-chest situation. The animals in ATO group were pretreated with ATO for 7 d and continued during tachypacing. Serial atrial effective refractory period（ AERP） was measured in each rabbit at baseline,8 h,16 h,24 h,32 h,40 h and 48 h with different cycle lengths. The changes of cardiac functions and cardiac structure were observed by cardiac ultrasonic cardiogram before and after atrial tachypacing. The expression of atrial ion channel proteins Ca Lα1 and Kv4. 3 was detected by Western blotting. RESULTS： Compared with NP group,AERP at cycle lengths of 150 and 200 ms,the adaption of AERP,and the levels of Ca Lα1 and Kv4. 3 expression were all decreased in ATP and ATO group,especially in ATP group. Left atrial dimension（ LAD） was increased in pacing groups as compared with NP group（ P 0. 05） after pacing delivery for 48 h,while no difference between the formers was observed. No significant change of the left ventricular dimension（ LVD） and ejection fraction（ LVEF） among groups before and after pacing was found. CONCLUSION： Atrial tachypacing significantly shorten AERP,resulting in poor adaption of AERP,while ATO pretreatment significantly attenuates the atrial electrical remodeling in rabbits,but had no effect on cardiac structure. ATO suppresses the down-regulation of atrial ion channel proteins Ca Lα1 and Kv4. 3 expression after48 h,which may be the potential ionic mechanism of atrial electrical remodeling for ATO.