地尔硫卓对猪急性心肌梗死再灌注后无再流的影响

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

目的评价地尔硫卓防治猪急性心肌梗死(AMI)再灌注后无再流的作用。方法实验动物随机分成对照组、地尔硫卓组(2mg/min冠脉内)和假手术组。前两组行冠状动脉结扎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。结果与AMI前相比,对照组AMI后3h、左室收缩压(LVSP)、心排量(CO)和左心室内压最大收缩和舒张变化速率(±dp/dtmax)均显著下降(均P<0.05,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),然而±dp/dtmax继续显著下降(P<0.05);而地尔硫卓组AMI后3h各项指标变化与对照组相同;但再灌注后1h LVEDP、±dp/dtmax和CO均显著恢复(均P<0.05),且比对照组更显著(均P<0.05)。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),再灌注后无再流范围(ANR)分别为78.5%和82.3%,心肌坏死范围(NA)占LA的98.5%;而地尔硫卓组两方法所测LA均与对照组相当(均P>0.05),但ANR仅分别为20.6%和19.9%,NA又与对照组差异无统计学意义(P>0.05)。对照组再灌注即刻和再灌注后1h冠脉血流量仅占AMI前的45.8%和50.6%(均P<0.01),而地尔硫卓组冠脉血流量分别提高到80.4%和79.3%,比对照组增加均有统计学意义(均P<0.01)。

Objective To evaluate the beneficial effects of diltiazem on myocardial no-reflow.Methods Twenty-four mini-swine were randomized into 3 equal groups: diltiazem-treated group subjected to 3 hours of coronary occlusion to cause acute myocardial infarction (AMI), followed by 60 minutes of reperfusion and injected with diltiazem into the coronary artery 1 minute before reperfusion, control group undergoing coronary occlusion followed by 60 minutes of reperfusion and injected with normal saline, and sham operation group. 5 minutes before AMI in all groups and 180 minutes after AMI and 60 minutes after re-perfusion in the diltiazem and control groups, hemodynamic data, such as heart rate (HR), left ventricular systolic pressure (LVSP). Left ventricular end diastolic pressure (LVEDP),±dp/dt_~max , cardiac output (CO), and coronary blood volume (CBV) were measured. Myocardial contrast echography (MCE) was used to measure the left ventricle wall area(LVWA)and ligation area (LA) so as to calculate LA and to measure the area of no-reflow (ANR)so as to calculate ANR. 60 minutes after reperfusion thioflavin-S was injected into left ventricle so as to color the reperfused area and then the descending anterior branch was re-ligated and Evan′s blue was injected into the left ventricle to color the area outside the ligation area. The heart was taken out to undergo histological examination.Results (1) In comparison with the values before AMI the LVSP, ±dp/dt_~max , and CO of the control group significantly declined (P<0.05,0.01), while the LVEDP significantly increased (P<0.01) by the end of 3 hours after LAD occlusion; and the LVSP significantly increased and the ±dp/dt_~max further significantly declined (both P<0.05) 60 minutes after reperfusion. In the diltiazem 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, while the ±dp/dt_~max , CO, and LVEDP recovered significantly, more significantly than those in the control group, 60 minutes after reperfusion (all P<0.05).(2)In the control group, the sizes of coronary ligation area (LA) measured by both MCE in vivo and histopathological evaluation were similar (P>0.05), and the values of area of no-reflow (ANR) measured by MCE in vivo and histopathological evaluation were 78.5% and 82.3% respectively with the final necrosis area (NA) reaching 99% of the LA. There was no significant difference in LA measured by both MCE and histopathological evaluation between the control and diltiazem groups, while the values of ANR measured by both methods was significantly decreased to 19.9% and 20.6% that before AMI respectively in the diltiazem group (both P<0.01). There was no significant difference in NA between the control and diltiazem groups (P>0.05). The CBV of the control group was significantly declined to 45.8% and 50.6% of the baseline value respectively immediately and 60 minutes after reperfusion (both P<0.01), while the CBV of the diltiazem group became 80.4% and 79.3% of the baseline value respectively immediately and 60 minutes after reperfusion (both P<0.05), both significantly higher than those of the control group (both P<0.01).Conclusion Diltiazem is effective both in preventing myocardial no-reflow and improving left ventricular function, but not in reducing MI size during AMI and reperfusion.