卡维地洛对急性心肌梗塞后晚期心室重构影响的实验研究

Experimaental study of carvedilol on late ventricular remodeling after acute myocardial infarction

目的：观察卡维地洛对大鼠急性心肌梗塞后8周心室重构、血清Ⅲ型胶原氨基末端肽（PⅢNP）水平及左心室功能的影响。方法：结扎雄性大鼠左前降支建立急性心肌梗塞模型．术后24h存活的大鼠16只被随机分为：对照组（n=8）、卡维地洛组（n=8，10mg／kg·d，灌胃给药）；另设假手术组（n=8）。术后8周导管法测量血流动力学及左心室功能，形态学测算梗塞面积、左心室扩张指数和球形指数；Masson三色染色测量非梗塞区（NIZ）胶原容积分数（CVF）；放免法测量PⅢNP水平。结果：对照组与卡维地洛组大鼠梗塞面积无显著性差异（44．70％vs 41．79％）。与假手术组相比，对照组左心室舒张末压（LVEDP），左、右心室相对重量（LVRW、RVRW），室间隔厚度（IVST），左心室扩张指数（LVDI），左心室NIZ的CVF、PⅢNP水平均显著增加（P〈0．01～0．001）；血压、左心室收缩压（LVSP）、左心室球形指数（LVSI）、左心室内压最大上升和下降速度（±dp／dtmax）及其校正值（±dp／dtmax／LVSP）均显著降低（P〈0．01～0．001）。与对照相比，卡维地洛组心率、LVEDP、LVRW、RVRW、IVST、LVDI、非梗塞区CVF、PⅢNP水平显著降低（P〈0．01～0．001）；LVSI、±dp／dtmax及其校正值（±dp／dtmax／LVSP）显著升高（P〈0．01～0．001）。血清PⅢNP含量与LVEDP水平呈显著正相关（r=0．8628，P（0．001）。结论：卡维地洛能有效抑制急性心肌梗塞后左心室非梗塞区胶原增生，减轻大鼠急性心肌梗塞后的左心室重构，改善血流动力学和左心室功能。

Objective： To observe changes of ventricular remodeling, serum amino-terminal propepitide of type Ⅲ procollagen （P Ⅲ NP） levels and left ventricular function after acute myocardial infarction in rats with carvedilol intervention. Methods： After ligating left anterior descending artery 24 h, 16 surviving male Sprague-dawley （SD） AMI rats were randomly assigned to control （n = 8）,carvediol group （n = 8,10 mg/kg·d by gastric gavage）. Eight sham-operated rats were selected as non-infarcted control group. After 8 weeks of drug therapy ,hemodynamics and left ventricular function were measured by catheterization ; infarcted area, left ventricular dilatation index （LVDI） and sphericity index （LVSI） were measured and calculated using morphological methods; the hearts were stained with Masson trichrome for analysis of collagen volume fraction （CVF） in the non-infarcted zone （NIZ） ; serum concentrations of PⅢNP were measured by radiommunoassay method. Results： There were no significant differences in MI size between two AMI groups （44.70% vs. 41.79%）. Compared with the sham-operated group, left ventricular end diastolic pressure （LVEDP）, left and right ventricular relative weight （LVRW, RVRW）, thickness of interventricular septum （IVST）, LVDI, CVF in the NIZ and serum concentrations of P Ⅲ NP were all significantly increased （P〈0. 01～0. 001 ）in control group, while blood pressure （BP）,left ventricular systolic pressure （LVSP）,LVSI, the left ventricular pressure maximal rate of rise and fall （±dp/dtmax） and their adjustments by LVSP （±dp/dtmax/LVSP） were significantly decreased （P〈0. 01 ～0. 001 ）. Compared with the control group, the heart rate, LVEDP, LVRW, RVRW, IVST, LVDI. CVF in NIZ, serum concentrations of P Ⅲ NP were significantly decreased （P〈0.01～0. 001）, while LVSI, ±dp/dtmax and ±dp/dtmax/LVSP were all significantly increased （P〈0.01～0. 001） in the carvedilol group. The serum concentrations of P Ⅲ NP were positively correlated to the levels of LVEDP （r= 0. 8628. P〈0. 001 ）. Conclusion ： Carvedilol can effectively decrease collagen proliferation in the NIZ of LV, prevent left ventricular remodeling and improve hemodynamics and LV function in AMI rats.