氯沙坦、依那普利及其联合用药对大鼠急性心肌梗死后左心室重构预防作用的比较。

Comparison of the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling after acute myocardial infarction in the rat.

作者信息

Yuejin Yang, Pei Zhang, Yingmao Ruan, Laifeng Song, Xinglin Xu, Yongli Li, Yanwen Zhou, Yi Tian, Yishu Xu, Zaijia Chen

机构信息

Division of Coronary Heart Disease, Cardiovascular Institute and Fu Wai Hospital, CAMS & PUMC, Beijing 100037.

出版信息

Chin Med Sci J. 2002 Dec;17(4):236-41.

PMID:12901512

Abstract

OBJECTIVES

To compare the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat.

METHODS

AMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups : 1) AMI control group (n = 19), 2) losartan group (n = 22, 3 mg x kg(-1) x d(-1)), 3) enalapril group (n = 20, 1 mg x kg(-1) x d(-1)), 4) losartan-enalapril combinative group (n = 22, 3 and 1 mg x kg(-1) x d(-1) respectively). 5) Sham-operated group (n = 10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1) AMI controls (n = 11), 2) losartan group (n = 10), 3) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11), 5) sham-operated group (n = 6) and 6) normal controls (n = 8).

RESULTS

There were no significant differences among the 4 AMI groups in MI size (41.7% to approximately 43.4%, all P > 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW) in AMI group were all significantly increased (P < 0.05 to approximately 0.001); whereas the maximum left ventricular pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were significantly reduced (all P < 0.001), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased (P < 0.05 to approximately 0.001); while +/- dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P < 0.05 to approximately 0.001) except -dp/dt/LVSP in losartan group (P > 0.05). There were no significant differences in the above indices among the 3 treatment groups (all P > 0.05).

CONCLUSION

Both losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination.

摘要

目的

比较氯沙坦、依那普利及其联合应用对大鼠急性心肌梗死（AMI）后左心室重构（LVRM）的预防作用。

方法

通过结扎左冠状动脉在雌性SD大鼠中诱导建立AMI模型。术后48小时，将83只存活大鼠随机分为以下4组之一：1）AMI对照组（n = 19），2）氯沙坦组（n = 22，3 mg·kg⁻¹·d⁻¹），3）依那普利组（n = 20，1 mg·kg⁻¹·d⁻¹），4）氯沙坦 - 依那普利联合组（n = 22，分别为3和1 mg·kg⁻¹·d⁻¹）。随机选取5）假手术组（n = 10）和6）正常大鼠组（n = 10）作为非梗死对照。氯沙坦和依那普利通过直接灌胃给药。药物治疗4周后，对每组进行血流动力学研究，然后用10%福尔马林固定大鼠心脏并进行病理分析。在56只大鼠中获得了完整的实验数据，包括1）AMI对照组（n = 11），2）氯沙坦组（n = 10），3）依那普利组（n = 10），4）氯沙坦与依那普利联合组（n = 11），5）假手术组（n = 6）和6）正常对照组（n = 8）。

结果

4个AMI组之间梗死面积无显著差异（41.7%至约43.4%，所有P > 0.05）。与假手术组相比，AMI组的左心室（LV）舒张末期压力（LVEDP）、容积（LVV）、长轴和短轴长度（L和D）以及LV绝对和相对重量（LVAW和LVRW）均显著增加（P < 0.05至约0.001）；而左心室最大压力上升和下降速率（±dp/dt）及其经LV收缩压校正的值（±dp/dt/LVSP）显著降低（所有P < 0.001），表明AMI后发生了LVRM且LV收缩和舒张功能受损。与AMI组相比，所有3个治疗组的LVEDP、LVV、LVAW和LVRW均显著降低（P < 0.05至约0.001）；而除氯沙坦组的 -dp/dt/LVSP外（P > 0.05），所有3个治疗组的±dp/dt/LVSP均显著增强（P < 0.05至约0.001）。3个治疗组之间上述指标无显著差异（所有P > 0.05）。