不同剂量卡维地洛防治大鼠急性心肌梗死左室重构的研究

目的对比观察不同剂量卡维地洛对大鼠急性心肌梗死(AMI)左室重构(LVRM)的防治作用。方法雌性SD大鼠AMI术后成活142只，分为AMI对照组(n=35)，和卡维地洛大剂量(10mg·kg-1·d-1，n=37)，中剂量(1mg·kg-1·d-1，n=35)，及小剂量(0.1mg·kg-1·d-1，n=35)四组。另设假手术组对照。直接灌胃给药4周后行血流动力学测定、心脏标本固定及病理分析。去除梗死面积＜35％或＞55％者，最终58只大鼠资料完整。结果AMI各组间梗死面积均无显著差异(44.5％～46.3％，P均＞0.05)。与假手术组相比，AMI组的左室舒张末压(LVEDP)、容积(LVV)、实际左心室重量(LVAW)及相对重量(LVRW)均显著增加(P均＜0.01)，左室球形指数和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＜0.01)。与AMI组相比，卡维地洛大、中、小剂量组的LVEDP、LVV、LVAW和LVRW均呈剂量相关性显著降低(LVEDP7.7mmHg±1.9mmHg，12.1mmHg±2.0mmHg，14.5mmHg±4.6mmHg对24.5mmHg±5.3mmHg；LVV0.72ml±0.10ml,0.79ml±0.08ml,0.82ml±0.10ml对0.92ml±0.11ml；LVAW589mg±57mg,622mg±70mg，666mg±57mg对730mg±79mg；P＜0.05～0.001)，±dp/dt及±dp/dt/LVSP均显著增加(P＜0.05～0.01)，但各剂量组间均无显著差异，左室球形指数仅在大剂量组显著改善(P＜0.05)。结论卡维地洛大、中、小剂量均能有效地防止大鼠AMI左室重构，改善血流动力学和左室功能；小剂量有效，大剂量更好。

Comparative effects of carvediol in large, middle, and small dose in preventing left ventricular remodeling after acute myocardial infarction in rats

OBJECTIVE: To compare the effects of carvedilol in large, middle, or small dose in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats. METHODS: AMI were conducted by ligating left coronary artery in female SD rats. Twenty-four hours after the procedure, 142 surviving rats were randomly assigned to one of the following groups: AMI control (n = 35), large dose carvedilol (10 mg.kg-1.d-1, n = 37), middle dose carvediol (1 mg.kg-1.d-1, n = 35), and small dose carvediol(0.1 mg.kg-1.d-1, n = 35) Sham-operated rats (n = 16) were selected randomly as non-infarction control. Carvedilol was administered by direct gastric gavage for four weeks. Then hemodynamic studies were performed, and the hearts of the rats were taken out and fixed with 10% formalin and pathologic analysis was performed. Exclusive of the rats with infarct size < 35% or > 55%, complete experimental variables were obtained in 58 rats. RESULTS: No significant difference was found in MI size (44.5-46.3%, all P > 0.05) among the four AMI groups. Compared with the sham-operated group, a significant increase could be seen in left ventricular end diastolic pressure (LVEDP, 24.5 mm Hg +/- 5.3 mm Hg), left ventricular volume (LVV, 0.92 ml +/- 0.11 ml), left ventricular absolute weight (LVAW, 730 mg +/- 79 mg) and left ventricular relative weight (LVRW) (LVEDP: vs.; LVV: vs.; LVAW: vs. 730 mg +/- 79 mg; P < 0.05-0.001), and a significant decrease could be seen in sphericity index and LV pressure maximal rate of rise and fall (+/- dp/dt) as well as their corrected values (+/- dp/dt/LVSP) among AMI groups (P < 0.01-0.001). In comparison with AMI groups, a dose-dependent and significant decrease could be seen in LVEDP (7.7 mm Hg +/- 1.9 mm Hg, 12.1 mm Hg +/- 2.0 mm Hg, 14.5 mm Hg +/- 4.6 mm Hg), LVV(0.72 ml +/- 0.10 ml, 0.79 ml +/- 0.08 ml, 0.82 ml +/- 0.10 ml), LVAW (589 mg +/- 57 mg, 622 mg +/- 70 mg, 666 mg +/- 57 mg) and LVRW among large, middle, and small dose carvediol groups (all P < 0.01), while a significant increase could be seen in +/- dp/dt and +/- dp/dt/LVSP (all P < 0.05-0.01) among the three carvedilol groups without significant difference among different doses. The sphericity index was significantly increased only in large-dose carvedilol group (1.71 +/- 0.19 vs 1.96 +/- 0.25, P < 0.05). CONCLUSION: Carvedilol in no matter what dose effectively and dose-dependently prevent LV remodeling after AMI and improve hemodynamics and LV function in rats.