应用压力-容积环评价曲美他嗪对大鼠心肌顿抑的影响

Effect of Trimetazidine on Myocardial Stunning by Pressure-volume Loops in Rats

目的应用压力-容积环评价曲美他嗪对大鼠心肌顿抑的影响及可能机制。方法 30只雄性SD大鼠,随机等分成3组:对照组、心肌顿抑组(生理盐水2 mL)和曲美他嗪组(曲美他嗪片3 mg/kg)。结扎冠状动脉左前降支20 min再灌注120 min,制作大鼠心肌顿抑模型(对照组只穿线不结扎)。用压力-容积系统动态观察心率、左心室收缩期末压、收缩期末压力容积、左心室舒张期末压及舒张期末压力容积等血流动力学变量以及压力-容积环变化,并应用软件PowerLab系统离线分析;再灌注结束后测定大鼠心肌组织中ATP含量、ATP酶活性及磷酸果糖激酶活性,并应用体视学方法定量分析大鼠心肌线粒体的变化。结果与心肌顿抑组相比,曲美他嗪组舒张期末压、收缩期末容积、前负荷补充搏功均显著降低(P<0.01),舒张期末压力-容积也降低(P<0.05);舒张期末容积、收缩期末压力容积均显著升高(P<0.01),ATP含量及ATP酶(Ca2+-Mg2+ATPase和Na+-K+ATPase)活性增加(P<0.05);磷酸果糖激酶活性显著增加(P<0.01);心肌线粒体损伤显著减轻(P<0.01)。结论曲美他嗪可以通过改善能量代谢降低心肌顿抑的发生,压力-容积环能准确敏感地评价心功能。

Aim To evaluate the effect of trimetazidine on myocardial stunning by pressure-volume loops in rats and its probable mechanism. Methods Thirty SD rats were randomly divided into 3 groups equally,control group and myocardial stunning group （physiological saline 2 mL）, trimetazidine group （trimetazidine tablet 3 mg/kg）. All rats, ex- cept for those in control group, were subjected to 20 minutes of left anterior descending artery occlusion and 120 minutes reperfusion, while in control group only threading without ligation. Hemodynamic variables （ as heart rate, left ventricular end-diastolic pressure, left ventricular end-systolic pressure and so on） were dynamicly observed by the pressure-volume loops and PowerLab system and software offline were applicated to analyse. Myocardial tissue ATP content, ATPase activ- ity and phosphate fructokinase （PFK） activity were detected after reperfusion for 120 min, and myocardial mitochondria ul- trastructure was tested using the electron microscope by stereology method. Results Compared with myocardial stun- ning group, in trimetazidine group, end-diastolic pressure（ EDP）, end-systolic volume （ESV） and preload recruited stroke work （PRSW） were significantly reduced （P 〈 0.01 ）, end-diastolic pressure-volume （EDPVR） were also decreased （P 〈 0.05 ）. End-diastolic volume （EDV） and end-systolic pressure-volume （ESPVR） were obviously increased by pressure volume ring analysis. ATP content and ATPase activity elevated （Ca~~ -Mg2~ ATPase and Na~ -K~ ATPase, P 〈 0.05 ） ; PFK activity added（P 〈 0.01 ） ; and myocardial mitochondria ultrastructure significantly ameliorated abnormal changes （P 〈 0.01 ）. Conclusions Trimetazidine attenuates myocardial stunning by the energy metabolism, and pressure volume ring can evaluate cardiac function accurately and sensitively.