Yang Yuejin, Tang Yida, Ruan Yingmao, Li Yongli, Zhou Yanwen, Gao Runlin, Chen Jilin, Chen Zaijia
Cardiovascular Institute & Fu Wai Heart Hospital, Chinese Academy of medical Science & Peking Union Medical College, Beijing, China.
J Renin Angiotensin Aldosterone Syst. 2002 Mar;3(1):31-5. doi: 10.3317/jraas.2002.005.
To compare the effects of cilazapril, carvedilol and their combination in preventing left ventricular remodelling (LVRM) after acute myocardial infarction (AMI) in rats.
Twenty-four hours after left coronary artery ligation, 100 surviving AMI female Sprague-Dawley rats were randomly assigned to: (1) AMI control (n=25); (2) cilazapril (Cila, 1 mg/kg/day) (n=25); (3) carvedilol (Car, 1 mg/kg/day) (n=25), and (4) cilazapril (1 mg/kg/day)+ carvedilol (1 mg/kg/day) (combination) (n=25) groups. A sham-operated group (n=17) was selected randomly as a non-infarction control. After four weeks of therapy with the drugs given by gastric gavage, haemodynamic studies were performed, following which the rat hearts were fixed and pathologically analysed. Rats with MI size <35% or >55% were excluded. Complete data were obtained in 64 rats, comprising AMI control (n=13), Cila (n=12), Car (n=12), Combination (n=14), and sham-operated (n=13) groups.
There were no significant differences in MI size between the four AMI groups (45.2 46.7%, p>0.05). Compared with the 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<0.001) in the AMI group, while the LV pressure maximal rate of rise and fall ( dp/dt) was significantly decreased (all p<0.001). In comparison with the AMI group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased, while dp/dt was significantly increased in the Cila, Car, and combination groups, with LVEDP and STh decreasing more in the combination group than in the two monotherapy groups (p<0.05 0.01). There were no significant differences in other variables between the three therapy groups.
Cilazapril, carvedilol and their combination are all effective in preventing LVRM after AMI in rats, and in improving haemodynamics and LV function, with the combination therapy being superior to monotherapy in all respects.
比较西拉普利、卡维地洛及其联合用药对大鼠急性心肌梗死(AMI)后左心室重构(LVRM)的预防作用。
左冠状动脉结扎24小时后,将100只存活的AMI雌性Sprague-Dawley大鼠随机分为:(1)AMI对照组(n = 25);(2)西拉普利(Cila,1 mg/kg/天)组(n = 25);(3)卡维地洛(Car,1 mg/kg/天)组(n = 25),以及(4)西拉普利(1 mg/kg/天)+卡维地洛(1 mg/kg/天)联合用药组(n = 25)。随机选取一组假手术组(n = 17)作为非梗死对照组。经胃管给予药物治疗四周后,进行血流动力学研究,随后将大鼠心脏固定并进行病理分析。梗死面积<35%或>55%的大鼠被排除。在64只大鼠中获得了完整数据,包括AMI对照组(n = 13)、Cila组(n = 12)、Car组(n = 12)、联合用药组(n = 14)和假手术组(n = 13)。
四个AMI组之间的梗死面积无显著差异(45.2%至46.7%,p>0.05))相比),AMI组的左心室(LV)舒张末期压力(LVEDP)、容积(LVV)、重量(LVW)、室间隔厚度(STh)和右心室重量(RVW)均显著增加(均p<0.001),而左心室压力最大上升和下降速率(dp/dt)显著降低(均p<0.001)。与AMI组相比,Cila组、Car组和联合用药组的LVEDP、LVV、LVW、STh和RVW均显著降低,而dp/dt显著增加,联合用药组的LVEDP和STh降低幅度大于两个单药治疗组(p<0.05至0.01)。三个治疗组之间其他变量无显著差异。
西拉普利、卡维地洛及其联合用药均能有效预防大鼠AMI后的LVRM,并改善血流动力学和左心室功能,联合治疗在各方面均优于单药治疗。