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.