卡维地洛防治大鼠急性心肌梗死左室重塑的作用

Comparative effects of carvedilol,losartan and cilazapril on preventing left ventricular remodeling after acute myocardial infarction in rats

目的 评价第三代 β 受体阻滞剂卡维地洛防治大鼠急性心肌梗死 (AMI)左室重塑(LVRM)的作用。方法 10 0只雌性SD大鼠AMI术后 2 4h随机分成 :(1)AMI对照组 (n =2 5 ) ;(2 )卡维地洛组 (n =2 5 ) (1mg·kg-1·d-1) ;(3)西拉普利组 (n =2 5 ) (1mg·kg-1·d-1)和 (4)氯沙坦组 (n =2 5 )(3mg·kg-1·d-1) ;另设假手术组 (n =17)。治疗组直接灌胃给药。 4周后行血流动力学测定 ,心脏标本固定和作病理学分析。去除心肌梗死面积 <35 %或 >5 5 %者 ,最终资料完整大鼠 6 3只 ,在以上各组分别为 13、12、12、13和 13只大鼠。结果 AMI各组间梗死面积差异均无显著性 (45 8%～ 4 6 7% ,P均 >0 0 5 )。与假手术组相比 ,AMI组的左室舒张末压 (LVEDP)、容积 (LVV)、重量 (LVW )、室间隔厚度 (STh)和右室重量 (RVW)均显著增加 (P均 <0 0 0 1) ,左室内压最大上升和下降速率 (±dp/dt)及其校正值 (±dp/dt/LVSP)均显著降低 (P均 <0 0 0 1)。与AMI组相比 ,卡维地洛、西拉普利和氯沙坦组的LVEDP和LVV均显著降低 (P <0 0 1～ 0 0 0 1) ,室间隔厚度均显著减小 (P <0 0 0 1) ;LVW和RVW均显著减轻 (P <0 0 5～ 0 0 1) ,±dp/dt及±dp/dt/LVSP均显著升高 (P <0 0 5～ 0 0 0 1)。

Objective To compare the effects of the third generation β blocker carvedilol with losartan and cilazapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats Methods Twenty four hours after ligating left coronary artery, 100 surviving AMI female Sprague Dawley rats were randomly divided into 4 groups: (1)AMI control( n =25), (2) carvedilol 1 mg·kg -1 ·d -1 (C1, n =25); (3) cilazapril 1 mg·kg -1 ·d -1 (C2, n =25), and (4) losartan 3 mg·kg -1 ·d -1 (L3, n =25) Sham operated group ( n =17) were selected randomly as non infarction control After 4 weeks of drug therapy by gavage, hemodynamic studies were performed, then the rat hearts were fixed and pathologically analyzed The rats with MI size <35% or >55% were excluded The complete data were obtained in 63 rats with 13 in AMI control, 12 in C1, 12 in C2, 13 in L3, and 13 sham operated groups Results There were no significant differences in MI size among the four AMI groups [(45 8～46 7)%, all P >0 05] Compared with sham operated group, left ventricular end diastolic pressure (LVEDP),volume (LVV), weight (LVW), septal thickness (STh )and right ventricular weight (RVW)were all significantly increased (all P <0 001)in AMI group, while the maximal rate of left ventricular pressure rise and fall (±dp/dt)was significantly decreased (both P <0 001) In comparison with AMI control group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased( P <0 01～0 001) in C1, C2 and L3 groups, while ±dp/dt were significantly increased ( P <0 05～0 001); LVEDP decreased more in L3 group than in C1 group ( P <0 05), but there were no significant differences in other variables among the three therapeutic groups (all P >0 05) Conclusion Carvedilol has a similar effect as cilazapril and losartan on preventing LVRM after AMI in rats, which is worth studying further