中药通心络对猪急性心肌梗死再灌注后无再流的影响

Beneficial effects of Tong-xin-luo (herb) on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment of mini-swine model

目的评价通心络防治猪急性心肌梗死(AMI)再灌注后无再流的作用。方法中华小型猪40只随机分成5组,每组8只:(1)AMI模型对照组(对照组),(2)通心络小剂量治疗组(0·05g·kg-1·d-1),(3)通心络中剂量治疗组(0·2g·kg-1·d-1),(4)通心络大剂量治疗组(0·5g·kg-1·d-1),(5)假手术组。通心络各组预给药3d后行冠状动脉结扎180min,松解60min制备AMI再灌注模型。AMI前、后和再灌注后均行血流动力学测定,心肌声学造影(MCE)检查和病理学分析。结果(1)与AMI前相比,对照组AMI后180min左室收缩压(LVSP)、心排量和左心室内压最大收缩和舒张变化速率(±dp/dtmax)均显著下降(P<0·05或P<0·01),左室舒张末压(LVEDP)显著升高(P<0·01);再灌注后60min仅LVSP显著恢复(P<0·05),然而±dp/dtmax继续显著下降(P<0·05)。小、中和大剂量通心络组AMI后180min各项指标变化与对照组相同;再灌注后60min仅大剂量通心络组LVEDP、±dp/dtmax和心排量均显著恢复(均P<0·05),且显著好于对照组(均P<0·05)。(2)对照组MCE和病理染色所测的冠脉结扎区心肌范围(LA)高度一致(P>0·05),再灌注后无再流区范围分别为78·5%和82·3%,心肌坏死面积占结扎区心肌面积的98·5%。3个通心络组LA与对照组相当(均P>0·05),但MCE和病理染色所测无再流范围在中及大剂量通心络组分别为41·1%、42·4%和24·1%、25·0%,坏死心肌范围分别为90·2%及81·2%,均显著小于对照组和小剂量组(P<0·05或P<0·01),大剂量组也显著小于中剂量组(P<0·05或P<0·01)。(3)对照组再灌注后即刻和再灌注后60min冠脉血流量仅占AMI前的45·8%和50·6%(均P<0·01),而大剂量通心络组冠脉血流量分别占AMI前的76·0%和73·5%,均显著高于对照组(均P<0·01)。结论通心络能有效地防治心肌梗死再灌注后无再流,缩小梗死面积;中剂量有效,大剂量更好。

Objective To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion.Methods Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g·kg -1·d -1 for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g ·kg -1·d -1 for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g·kg -1·d -1 for 3 days), and sham-operation group.The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion.Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (±dp/dt max), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4.Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4.Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA.Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR.necrosis area (NS), and NA.Results (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, ±dp/dt max, and CO significantly decreased (P<0.05 or P<0.01), while LVEDP significantly increased (P<0.01) 3 hour after AMI, and then LVSP was significantly recovered while ±dp/dt max further significantly decreased (both P<0.05) 60 minutes after reperfusion.In the 3 Tongxinluo groups, the changes of LVSP, ±dp/dt max, CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, ±dp/dt max, CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P<0.05).(2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P>0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS.There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P<0.05 or P<0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P<0.05 and P<0.01).The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P<0.05).In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P<0.01).In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P<0.05), however, both significantly higher than those in the control group (both P<0.01).Conclusion Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.