Yang Yuejin, Tang Yida, Ruan Yingmao, Wang Yanwu, Gao Runlin, Chen Jilin, Chen Zaijia
Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jpn Heart J. 2003 Nov;44(6):979-88. doi: 10.1536/jhj.44.979.
The dose-related beneficial effects of carvedilol on survival in heart failure have been verified, however, the effects on left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) have not been defined. This experiment was designed to compare the effects of low, middle, and high doses of carvedilol (LD-car, MD-car, and HD-car) with metoprolol (Meto) in preventing postinfarction LVRM in rats. After the left coronary artery was ligated, 177 surviving female SD rats were randomized to: (1) AMI (n = 35), (2) LD-car (0.1 mg x kg(-1) x d(-1), n = 35), (3) MD-car (1 mg x kg(-1) x d(-1), n = 35), (4) HD-car (10 mg x kg(-1) x d(-1), n = 37) and (5) Meto (2 mg x kg(-1) x d(-1), n = 35) groups. A sham-operated group (n = 16) was also randomly selected. Gastric gavage therapy lasted for 4 weeks. After hemodynamic studies, the rat hearts were fixed and pathologically analyzed. After exclusion of rats which died or had an infarct size < 35% or > 55%, complete data were obtained in 69 rats, comprising AMI (n = 11), LD-car (n = 11), MD-car (n = 12), HD-car (n = 12), Meto (n = 11) and sham (n = 12) groups. There were no significant differences in MI size among the five AMI groups (44.5-46.3%, all P > 0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased, while +/- dp/dt was significantly decreased in the AMI group (all P < 0.001). Compared with the AMI group, heart rate was significantly decreased in all except the LD-car treatment groups (P < 0.05-0.01); LVEDP, LVV, LVW, and STh in the four treatment groups were also significantly decreased (P < 0.05-0.001) except LVW and STh in the Meto group (both P > 0.05)(LVEDP: 14.5 +/- 4.6, 12.1 +/- 2.4, 7.7 +/- 1.9 and 13.0 +/- 6.7 mmHg vs 24.1 +/- 5.2 mmHg; LVV: 0.82 +/- 0.1, 0.79 +/- 0.1, 0.72 +/- 0.1 and 0.72 +/- 0.1 mL vs 0.92 +/- 0.1 mL; LVW: 666 +/- 57, 622 +/- 70, 589 +/- 57 and 699 +/- 78 mg vs 730 +/- 79 mg; STh: 1.14 +/- 0.12, 1.18 +/- 0.21, 1.19 +/- 0.15 and 1.35 +/- 0.20 mm vs 1.33 +/- 0.29 mm; P < 0.05-0.001); while +/- dp/dt was significantly increased in each therapy group (P < 0.05-0.001). There were dose-effect relations in LVEDP and LVV in the carvedilol groups. The results indicate that low, middle and high dose carvedilol has dose-related effects in the prevention of postinfarction LVRM with respect to volume expansion and segmental hypertrophy in rats, while metoprolol prevents only LV dilatation but not hypertrophy.
卡维地洛对心力衰竭患者生存的剂量相关有益作用已得到证实，然而，其对急性心肌梗死（AMI）后左心室重构（LVRM）的影响尚未明确。本实验旨在比较低、中、高剂量卡维地洛（LD - car、MD - car和HD - car）与美托洛尔（Meto）对大鼠心肌梗死后LVRM的预防作用。结扎左冠状动脉后，将177只存活的雌性SD大鼠随机分为：（1）AMI组（n = 35），（2）LD - car组（0.1 mg·kg⁻¹·d⁻¹，n = 35），（3）MD - car组（1 mg·kg⁻¹·d⁻¹，n = 35），（4）HD - car组（10 mg·kg⁻¹·d⁻¹，n = 37）和（5）Meto组（2 mg·kg⁻¹·d⁻¹，n = 35）。还随机选取了假手术组（n = 16）。灌胃治疗持续4周。进行血流动力学研究后，将大鼠心脏固定并进行病理分析。排除死亡或梗死面积<35%或>55%的大鼠后，在69只大鼠中获得了完整数据，包括AMI组（n = 11）、LD - car组（n = 11）、MD - car组（n = 12）、HD - car组（n = 12）、Meto组（n = 11）和假手术组（n = 12）。五个AMI组之间的梗死面积无显著差异（44.5 - 46.3%，所有P>0.05）。与假手术组相比，AMI组左心室（LV）舒张末期压力（LVEDP）、容积（LVV）、重量（LVW）和室间隔厚度（STh）均显著增加，而±dp/dt显著降低（所有P<0.001）。与AMI组相比，除LD - car治疗组外，所有组的心率均显著降低（P<0.05 - 0.01）；四个治疗组的LVEDP、LVV、LVW和STh也显著降低（P<0.05 - 0.001），但Meto组的LVW和STh除外（两者P>0.05）（LVEDP：14.5±4.6、12.1±2.4、7.7±1.9和13.0±6.7 mmHg vs 24.1±5.2 mmHg；LVV：0.82±0.1、0.79±0.1、0.72±0.1和0.72±0.1 mL vs 0.92±0.1 mL；LVW：666±57、622±70、589±57和699±78 mg vs 730±79 mg；STh：1.14±0.12、1.18±0.21、1.19±0.15和1.35±0.20 mm vs 1.33±0.29 mm；P<0.05 - 0.001）；而每个治疗组的±dp/dt均显著增加（P<0.05 - 0.001）。卡维地洛组的LVEDP和LVV存在剂量 - 效应关系。结果表明，低、中、高剂量卡维地洛在预防大鼠心肌梗死后LVRM的容量扩张和节段性肥厚方面具有剂量相关作用，而美托洛尔仅能预防左心室扩张，不能预防肥厚。
