卡维地洛、氯沙坦合用防治大鼠心肌梗死左室重构对比

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

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 (1mg·kg-1·d-1)、氯沙坦 (3mg·kg-1·d-1)和卡维地洛 (1mg·kg-1·d-1) +氯沙坦 (3mg·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 (4 5 8%～ 46 7%,P值均 >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值均 <0 0 1) ,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 0 1)。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 0 1) ,±dp/dt及±dp/dt/LVSP均显著升高 (P <0 0 5～ 0 0 1) ,且LVEDP和STh在合用组较卡维地洛组降低更显著 (P值均 <0 0 1)。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。

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·kg -1·d -1) (C1)(n=25); (3) losartan ( 3 mg·kg -1·d -1 ) (L3)(n=25); and(4)carvedilol (1 mg·kg -1·d -1)+losartan ( 3 mg·kg -1·d -1 ) (C1+L3)(n=25) groups. Sham-operated group (n=17) were selected rando mly 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 (allP<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.