卡维地洛、氯沙坦合用防治大鼠心肌梗死左室重构对比

目的对比卡维地洛、氯沙坦及其合用防治大鼠急性心肌梗死(AMI)左室重构(LVRM)的作用.方法雌性SD大鼠分为AMI对照、卡维地洛 (1 mg·kg-1·d-1)、氯沙坦(3 mg·kg-1·d-1)和卡维地洛(1 mg·kg-1·d-1)+氯沙坦(3 mg·kg-1·d-1)组,另设假手术组对照.给药4周后行血流动力学测定和病理分析.结果 AMI各组间梗死面积差异均无显著性(45.8%～46.7%,P值均>0.05).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值均<0.01),左室内压最大上升和下降速率(±dp/dp)及其校正值(±dp/dt/LVSP)均显著降低(P值均<0.01).与AMI组相比,卡维地洛、氯沙坦以及合用组的LVEDP、LVV、LVW、STh和RVW均显著降低或减轻(P值均＜0.01),±dp/dt及±dp/dt/LVSP均显著升高(P＜0.05～0.01),且LVEDP和STh在合用组较卡维地洛组降低更显著(P值均<0.01).结论卡维地洛和氯沙坦单用与合用均能有效抑制大鼠AMI后的左室重构,改善血流动力学和左室功能,且以合用更佳.

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

OBJECTIVE: To compare the effects of carvedilol, losartan and their combination in preventing from left ventricular remodeling (LVRM) after acute myocardial infarction(AMI) in rats. METHODS: Twenty-four hours after ligating left coronary artery, 100 surviving AMI female SD rats were randomly assigned to: (1) AMI control (n = 25), (2) carvedilol (1 mg x kg(-1) x d(-1)) (C1) (n = 25); (3) losartan (3 mg x kg(-1) x d(-1)) (L3)(n = 25); and (4) carvedilol (1 mg x kg(-1) x d(-1)) + losartan (3 mg x kg(-1) x d(-1)) (C1 + L3) (n = 25) groups. Sham-operated group (n = 17) were selected randomly as non-infarction control. After 4 weeks of therapy with the drugs by gastric gavage, hemodynamic studies were performed, then the rat hearts were fixed and pathologically analyzed. Exclusive of the rats with MI size < 35% or > 55%, complete data were obtained in 65 rats, which were comprised of AMI control (n = 13), C1 (n = 12), L3 (n = 13), C1 + L3 (n = 14) and sham-operated (n = 13) groups. RESULTS: There were no significant differences in MI size among the four AMI groups (45.8% - 46.7%, P > 0.05) . Compared with sham-operated group, Left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW), septal thickness (STh) and right ventricular weight (RVW) were all significantly increased (all P < 0.01 ) in AMI group, while the left ventricular pressure maximal rate of rise and fall (dp/dt) were significantly decreased (all P < 0.01). In comparison with AMI group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased (all P < 0.01), while +/- dp/dt and +/- dp/dt/LVSP were significantly increased (P < 0.05 - 0.01) in all three therapy groups, with LVEDP decreasing more in the combination and L3 groups than in C1 group (P < 0.05 - 0.01) and STh decreasing more in the combination group than in C1 group (P < 0.01), but there were no significant differences in other variables among the three therapy groups. CONCLUSION: Carvedilol, losartan and their combination all can prevent from LVRM after AMI in rats, improve hemodynamics and LV function, with the combination superior.