卡维地洛与美托洛尔对心肌梗塞后大鼠血流动力学的影响

Comparative effects of carvedilol and metoprolol on hemodynamics in rats after acute myocardial infarction

目的：研究比较卡维地洛与美托洛尔对大鼠心肌梗塞后血流动力学的影响。方法：结扎大鼠左冠状动脉建立急性心肌梗塞模型,术后24 h存活的147只SD大鼠以简单随机法分为心肌梗塞对照组（MI组,n=43）,美托洛尔（20mg/kg·d）治疗组（M组,n=42）,卡维地洛（10 mg/kg·d）治疗组（C组,n=42）,另设假手术组（S组,n=20）;各组按观察时点48 h和4周,再分为：MI组48 h和MI组4周,M组48 h和M组4周,C组48 h和C组4周,S组48 h和S组4周。M组、C组于术后24h直接灌胃法给药,并于术后48h及4周对相应的观察组进行血流动力学测定。结果：（1）与S 48h组相比,MI 48h组的主动脉收缩压（SBP）、舒张压（DBP）和平均压（MAP）、左心室收缩压（LVSP）和左心室内压最大上升和下降速率（±dp/dt）均显著降低（P〈0.05-〈0.01）;（2）与S 4周组比较,MI 4周组心率、LVSP和±dp/dt显著降低（P〈0.05-〈0.01）,左室舒张末压（LVEDP）则显著升高（P〈0.01）,而主动脉SBP、DBP和MAP无显著变化;（3）与MI 48h组相比,C48h组的SBP、MAP、LVSP、±dp/dt和心率均显著降低（P〈0.05-〈0.01）,LVEDP无显著变化,而M 48h组血流动力学指标均无显著差异;（4）与MI 4周组相比,C4周组SBP、DBP、MAP和LVEDP均显著降低（P〈0.05）,LVSP、±dp/dt等无显著变化;而M 4周组只有LVEDP和心率显著降低（P〈0.01）。结论：大鼠心肌梗塞后,可以发生血流动力学异常改变和左室功能异常。较长时间（4周）卡维地洛应用能有效降低AMI后大鼠左室舒张末压,改善血流动力学和左室功能,美托洛尔亦有相似作用。

Objective： To compare the effects Of carvedilol and metoprolol on hemodynamics in rats after acute myocardial infarction. Methods： AMI model was established with the ligation of anterior descending coronary artery in female SD rats. Twenty-four h after operation, 147 survivors were randomly assigned to AMI control （MI, n=43） group, metoprolol （20mg/kg·d） treatment （M, n=42） group, carvedilol （10mg/kg, d） treatment （C, n=42） group, while sham-operated rats （S, n=20） were selected randomly as non-infarction control. According to observation time, each group was subdivide into two subgroups： MI 48h group, MI 4 weeks group, M 48h group, M 4 weeks group, C 48h group, C 4 weeks group, S 48h group, S 4 weeks group. Metoprolol was given to group M and Carvedilol was given to group C by gastric garage at 24h after ligation. The hemodynamics of each group was studied at 48 hours and 4 weeks after ligation. Results： （1） Compared with sham-operated 48h group, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, mean aortic pressure （MAP）, left ventricular systolic pressure （LVSP） and the maximum rise rate of left ventricular pressure （dp/dt） significantly decreased （P〈0.05-〈0. 01）, while left ventricular end diastolic pressure （LVEDP） significantly increased （P〈0. 05） in Mt 48h group; （2） Compared with sham-operated 4 weeks group, heart rate, LVSP and dp/dt significantly decrease （P〈0. 05-〈0. 01）, while LVEDP was even obviously higher （P〈0. 01） in MI 4 weeks group; （3） Compared with MI 48h group, SBP, MAP, LVSP, dp/dt and heart rate significantly decreased in C48h group, while LVEDP does not change; There were all no change in M48h group; （4） Compared with MI4 weeks group, SBP, DBP, MAP, LVEDP notable decreased in C 4 weeks group （P〈0. 05） ; Only heart rate and LVEDP significantly decreased （P〈0. 01） in M 4 weeks group. Conclusion： Abnormal hemodynamics and left ventricular function developed after AMI in rats. Four weeks treatment of carvedilol can improve left ventricular function and hemodynamics. Metoprolol has equivalent benefieial effect as carvedilol.