[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).


CONCLUSIONS
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.
Zhao
Jing-lin
JL
Fuwai Heart Hospital, Beijing 100037, China.
Yang
Yue-jin
YJ
You
Shi-jie
SJ
Jing
Zhi-cheng
ZC
Wu
Yong-jian
YJ
Yang
Wei-xian
WX
Meng
Liang
L
Tian
Yi
Y
Chen
Ji-lin
JL
Gao
Run-lin
RL
Chen
Zai-jia
ZJ
D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology*; D020108:Nicorandil / Q000494:pharmacology*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D013556:Swine, Miniature
D020108:Nicorandil