尼可地尔对猪急性心肌梗死再灌注后无再流的影响

目的评价尼可地尔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24只,随机分成对照组、尼可地尔组和假手术组,每组8只。结扎冠状动脉(冠脉)3h、松解1h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和心肌声学造影(MCE)检查,最终行病理学分析。结果1与AMI前相比,对照组AMI后3h左室收缩压(LVSP)、心排血量(CO)和左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1h仅LVSP显著恢复(P<0.05),±dp/dtmax继续显著下降(P均<0.05)。尼可地尔组AMI后3h各项指标变化与对照组相同;但再灌注后1hLVSP、LVEDP、±dp/dtmax和CO均恢复,差异有显著性(P<0.05),且比对照组更显著(P均<0.05)。2对照组MCE和病理染色所测冠脉结扎区心肌范围(LA%)高度一致(P>0.05),再灌注后无再流范围(ANR%)分别为(78.50±4.35)%和(82.30±1.90)%,心肌坏死范围(NA%)为(98.50±1.35)%。尼可地尔组LA%虽与对照组相当(P均>0.05),但两方法所测ANR%和NA%均显著小于对照组(P<0.05或P<0.01)。3对照组再灌注即刻和再灌注后1h冠脉血流量(CBV)仅占AMI前的50.6%和45.8%(P均<0.01);尼可地尔组CBV分别提高到69.4%和67.9%,均比对照组显著增加(P均<0.01)。结论尼可地尔能有效防治AMI再灌注后无再流,改善其心功能,缩小梗死面积。

Beneficial effects of nicorandil on myocardial no-reflow state in a mini-swine model of acute myocardial infarction and reperfusion

OBJECTIVE: To evaluate the effects of nicorandil on myocardial no-reflow state in a mini-swine model of acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-four mini-swine were randomly divided into three study groups: 8 in control group, 8 in nicorandil-treatment group, and 8 in sham-operated group. Animals in the former two groups were subjected to 3 hours of coronary occlusion followed by 1 hour of reperfusion. Hemodynamics and coronary blood flow volume (CBV) were monitored, and the area of no-reflow (ANR) was evaluated with both myocardial contrast echocardiography (MCE) in vivo and pathological means. Necrosis area (NA) was measured with triphenyltetrazolium chloride (TTC) staining. RESULTS: (1)In control group, left ventricular systolic pressure (LVSP), the maximum change rate of left ventricular pressure rise and fall (+/-dp/dt max) and cardiac output (CO) significantly declined, while left ventricular end-diastolic pressure (LVEDP) significantly increased at the end of 3 hours of LAD occlusion compared to that prior to AMI (P<0.05 or P<0.01), and +/-dp/dt max further significantly declined, while LVSP significantly rose (all P<0.05) at 1 hour of reperfusion. In the nicorandil-treatment group, the changes of LVSP, +/-dp/dt max, CO and LVEDP were the same as those in the control group after 3 hours of AMI. In contrast, LVSP, +/-dp/dt max, CO and LVEDP significantly elevated at 1 hour of reperfusion, and the changes were more significant compared to those of the control group (all P<0.05). (2)In control group, the vascular area after coronary ligation (LA) as determined by MCE in vivo was consistent with that of pathological evaluation(P>0.05), and the range of ANR (ANR%) was also similar (78.50+/-4.35)% and (82.30+/-1.90)% respectively], with final range of NA (NA%) reaching (98.50+/-1.35% of LA. In the nicorandil-treatment group, there was no significant difference in the range of LA (LA%) for both MCE and pathological evaluation (P>0.05), which were also not significantly different from those in control group, while ANR% and NA% significantly decreased (P<0.05 or P<0.01). (3)In the control group, CBV was significantly declined to 50.6% and 45.8% of the baseline immediately after release of 3 hours occlusion and at 1 hour of reperfusion (both P<0.01). In the nicorandil-treatment group, CBV was also significantly declined immediately after release of 3-hour occlusion, and at 1 hour of reperfusion (both P<0.05), though it was significantly increased to 69.4% and 67.9% of the baseline, and they were both significantly higher than those in the control group (both P<0.01). CONCLUSION: Nicorandil is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area after coronary artery occlusion and reperfusion in mini-swine.