芪丹通脉片对缺血/再灌注犬心肌微血管功能的影响

Protective Effect of Qidan Tongmia Tablet on Myocardium Microvascular Flow during Ischemia-Reperfusion of Dogs by Myocardial Contrast Echocardiography

目的评价中药复方芪丹通脉片对急性缺血再灌注致心肌微血管功能的影响。方法应用12只健康犬,随机分为对照组(control)和芪丹通脉片治疗组(QDTMT treatment group),对照组经十二指肠给予生理盐水(1.5ml/kg),给药后30min分离冠状动脉左前降支,放置电磁流量计探头测定血流量,在其下缘左前降支1/2处结扎90min,松开后再灌注180min观察,分别于灌胃前、缺血90min和再灌注180min静脉快速均匀推入微泡声学造影剂SONOVUE,FLASH模式进行静脉声学造影,实时连续记录心肌声学造影前后的图像采用,采用Echopac图象工作站软件包进行分析心肌声学造影的图像视频密度,根据时间-视频密度曲线计算曲线下面积(area under curve,AUC)以评价心肌微血管的血流灌注状态,根据图像分析缺血心肌范围的影响。芪丹通脉片组则经十二指肠给予芪丹通脉片浸膏混悬液(1g/ml,1.5ml/kg),其余实验过程同对照组。并在不同时间点从冠状静脉窦采血,检测血清中NO和血浆中ET-1的含量。结果在基础状态、缺血前和缺血90min,对照组和芪丹通脉片干预组的时间-视频密度曲线计算曲线下面积(AUC)以及缺血后出现的灌注缺损所占左心室的百分比没有显著差异。然而再灌注180min两组的AUC存在显著差异(14.09±2.31 vs 11.47±1.55,P<0.05),左心室心肌灌流均没有完全恢复,但芪丹通脉片能够显著促进再灌注后心肌微循环灌流的恢复(92.10±2.2)%,与对照组(87.49±4.12)%比较,存在显著差异(P<0.05)。在缺血90min和再灌注180min,芪丹通脉片处理组血清中NO和血浆中ET-1分别为(68.98±10.01)μmol/L、(67.55±9.81)μmol/L和(114.73±11.89)μg/L,(139.97±12.36)μg/L,与对照组存在显著差异(56.38±8.27)μmol/L,(53.55±6.03)μmol/L和(137.40±13.48)μg/L,(161.90±19.14)μg/L,(P<0.05)。结论芪丹通脉片能够促进心肌缺血/再灌注后微循环血流的恢复,调节循环血中的NO和ET含量,改善微循环功能,抑制缺血/再灌注所致的心肌损伤。

Objective To investigate the effect of Qidan Tongmia tablet（QDTMT） on myocardial microvascular flow during ischemia-reperfusion using real-time myocardial contrast echocardiography （MCE）. Methods 12 anesthesia dogs were randomly divided into two groups of control group and QDTMT treatment group： the animal was anesthetized and the left anterior descending coronary artery （LDA） of open-chest animal was isolated for measuring blood flow with an electromagnetic flow probe, then the animal was subjected to 90min of LAD occlusion followed by 180min reperfusion after 30min of administrating saline in control. The real-time imaging with MCE by FLASH model was performed during baseline, 90min of ischemia and 180min of reperfusion . During ischemia reperfusion, the parameters of time-intensity curve were measured in corresponding regional myocardium. Area under curve（AUC） was fit and washing-in by Echopac software package; presence or absence of perfusion defects area by the MCE was calculated for the risk area and for control area and the perfusion area was expressed as ratio of myocardium perfusion area （MPA） and left ventricular wall area （ LVWA）. The contents of NO and ET in coronary sinus were measured at the time points. Results No difference in AUC and the ratio of MPA/LVWA by MCE was observed between the control and QDTMT-treatment group during baseline, pre-ischemia and 90min occlusion ; myocardium microvascular flow during reperfusion in QDTMT-treatment group was significantly better than control group during 180min reperfusion （ 14.09 ± 2.31 vs 11.47 ± 1.55 P 〈0.05） ; the myocardium perfusion area during 180 min reperfusion increased significandy in QDTMT-treatment group（92.10 ±2.2 % vs 87.49 ±4.12% in control, P〈0.05）, LAD blood flow during pre-ischemia in QDTMT-treatment was higher than baseline and control respectively（ P 〈 0.05）. The contents of NO and ET in coronary sinus during 90 and 180min were significantly different respectively（68.98 ± 10.01 μmol/L（67.55 ±9.81） μmol/L and （ 114.73 ± 11.89） μg/L, （ 139.97 ± 12.36） μg/L in QDTMT- treatment group vs （56.38 ±8.27）μmol/L （53.55 ±6.03）μmol/L and （137.40 ± 13.48）μg/L, （161.90 ± 19.14） μg/L in control P 〈0.05）. Conclusion QDTMT could promote the myocardium microvascular flow restoration during ischemia reperfusion and regulate the contents of NO an ET in coronary sinus against ischemia reperfusion injury.