大、中、小剂量依那普利防治大鼠AMI左室重构的作用对比

目的　对比大、中、小剂量依那普利(Enla)对大鼠AMI左室重构（LVRM）的防治作用,并评价其量效关系.方法　97只雌性SD大鼠,AMI术后48小时随机分成：（1）AMI对照,（2）Enla大剂量（10?mg*kg-1*d-1）,（3）Enla中剂量（1?mg*kg-1*d-1）和（4）Enla小剂量(0.1?mg*kg-1*d-1）四组.另设:(5)假手术和(6)正常组作对照.给药治疗4周后均行血流动力学测定、心脏标本固定及病理分析.最终67只大鼠获完整资料,在上述各组中的数目分别为13、13、12、12、8和9只.结果　AMI各组间梗塞面积均无显著差异（45.4%-47.4%，P均>0.05）.与假手术组相比,AMI组左室舒张未压(LVEDP)、容积(LVV)、长(L)、短(D)轴长度和左室实际(LVAW)及相对重量(LVRW)均显著增加(P均<0.001),发生了LVRM；而左室内压最大上升和下降速率(±dp/dt)及其校正值均显著降低(P<0.01-0.001).与AMI组相比,Enla大、中、小剂量三组的LVEDP、LVV、L以及LVAW和LVRW均显著降低或减小（P<0.05-0.001）,其中LVEDP、LVV、L和LVAW在大剂量组均比小剂量组降低或减小更显著(P均<0.05)；而±dp/dt校正值在大、中剂量二组显著恢复(P<0.05-0.01).结论　1.Enla大、中、小剂量均能有效防治AMI大鼠LVRM,且大剂量更优.2.Enla大、中剂量能明显改善AMI大鼠的左室功能,而小剂量则无效.

Comparison of three doses of enalapril in preventing left ventricular remodeling after acute myocardial infarction in the rat

Objective To compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.Methods AMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n=24), (2) high-dose (10?mg*kg-1*d-1, n=25), (3) middle-dose (1?mg*kg-1*d-1, n=23), and (4) low-dose (0.1?mg*kg-1*d-1, n=25) enalapril groups. In addition, sham-operated (n=13) and normal rats (n=10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size <35% or >55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n=13), (2) high-dose enalapril (n=13), (3)middle-dose enalapril (n=12), (4) low-dose enalapril (n=12), (5) sham-operated (n=8) and (6) normal (n=9) groups.Results There were no significant differences among the four AMI groups in infarction size (all P>0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P<0.001), while maximum LV pressure rising and dropping rates (±dp/dt) and their corrected values by LV systolic pressure (±dp/dt/LVSP) were all significantly reduced in the AMI control group (P<0.01-0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P<0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P<0.05), and the ±dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P<0.01). Conclusions High, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective.