卡维地洛与美托洛尔对AMI后大鼠血流动力学和左心室功能影响的对比研究

Comparison of effects on hemodynamics and left ventricular function in rats following acute myocardial infarction: carvedilol vs.metoprolol

目的对比研究卡维地洛与美托洛尔对大鼠心肌梗死后血流动力学、左心室功能的影响。方法建立大鼠急性心肌梗死模型,术后将大鼠随机分为心肌梗死对照组(MI组),美托洛尔治疗组(B组),卡维地洛治疗组(C组),另设假手术组(S组);各组按观察时点48h和4周再分为:MI组48h组和MI组4周组,B组48h组和B组4周组,C组48h组和C组4周组,S组48h组和S组4周组。B组、C组于术后24h直接灌胃法给药。于术后48h及4周对观察组进行血流动力学测定。结果①与S组48h组相比,MI组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或P<0.01)。②与S组4周组比较,MI组4周组心率、LVSP和±dp/dt显著降低(P<0.05或P<0.01),左室舒张末压(LVEDP)则显著升高(P<0.01),而SBP、DBP和MAP无显著变化。③与MI组48h组相比,C组48h组的SBP、MAP、LVSP、±dp/dt和心率均显著降低(P<0.05或P<0.01),LVEDP无显著变化,而B组48h组血流动力学指标差异均无显著性。④与MI组4周组相比,C组4周组SBP、DBP、MAP和LVEDP均显著降低(P<0.05),而±dp/dt、±dp/dt/LVSP显著升高(P<0.05或P<0.01);而B组4周组LVEDP和心率降低差异有显著性。结论大鼠心肌梗死后,发生血流动力学异常和左室功能异常。长时间(4周)应用卡维地洛或美托洛尔均能有效降低AMI后大鼠LVEDP,改善血流动力学和左室功能。但在改善左室功能方面卡维地洛更优于美托洛尔。

Objective To compare of the effects on hemodynamics and left ventricular function in rats after acute myocardial infarction （AMI） between carvedilol and metoprolol. Methods 147 models of AMI in rats were randomly assigned to myocardial infarction control group （MI group）, metoprolol group （group B） and carvedilol group （group C） following the ligation of anterior descending. Sham- operated rats were selected randomly as noninfarction control. According to observation time points, each group was subdivided into two groups： MI48h group, MI4W group, B48h group, B4W group, CA8h group, CAW group, S48h group, S4W group. Group B received intragastric metoprolol infusion and group C received intragastric carvedilol infusion at 24 hours after ligation. The hemodynamics in each group were measured at 48 hours and 4 weeks after ligation. Results （1）MI48h group had decreases in systolic blood pressure （SBP）, diastolic blood pressure （DBP）, mean aortic pressure （MAP）, left ventricular systolic pressure （LVSP） and the maximum rise and decline rate of left ventricular pressure （ ＋ dp/dt）, compared with S48h group, there were statistical significant differences （ P 〈0.05 or P 〈0.01）. （2）Compared with S4W group, the heart rate, LVSP and ＋ dp/dt in MI4W group decreased more significantly （ P 〈0.05 or P 〈0.01）, and left ventricular end diastolic pressure （LVEDP） elevated significantly （ P 〈0.01）, while SBP, DBP and MAP did not differed appreciably. （3） Compared with MI48h group, SBP, MAP, LVSP, ＋ dp/dt and heart rate in C48h group decreased significantly （ P 〈0.05 or P 〈0.01）, while LVEDP remained the same, the hemodynamic indices in tM8h group did not differ. （4）Compared with MI4W group, SBP, DI3P, MAP and LVEDP for CAW group decreased significantly （ P 〈0.05）, while ± dp/dt, ±dp/dt/LVSP elevated significantly （ P 〈0.05 or P 〈0. 01）, and LVEDP and heart rate for B4W group decreased significantly. Conclusion As abnormal hemodynamics and left ventricular function worsened after AMI in rats, long- term （four weeks） use of carvedilol or metoprolol can improve left ventricular function and hemodynamics, but carvedilol is superior to metoprolol in improving left ventricular function.