| Objective:To observe the effect of nicorandil on the no-reflow and infracted area in rats after acute myocardial ischemia reperfusion, assess changes in myocardial injury and fibrosis, and compare it with the effect of adenosine.Methods:48Male SD rats were randomized into sham operation group, control group,adenosine treatment group and nicorandil treatment group.For acute experiments,control group,adenosine treatment group and nicorandil treatment group were subjected ischemia for45minutes by ligation of curonary artery after thoracotomy and sequently reperfusion for120minutes to establish acute myocardial ischemia/reperfusion no reflow models.Sham operation group weren’t underwent occlusion of coronary artery. All rats were sacrificed after reperfusion for120minutes. Serum myocardial enzyme was tested after30minutes.Thioflavine S, Evans blue and Triphenyltetra zolium chloride(TTC)staining were performed to eveluate area of no reflow(ANR), infracted aera(IA),risk area(RA)of heart.For chronic experiments, control group, adenosine treatment group and nicorandil treatment group were subjected ischemia for45minutes by ligation of curonary artery after thoracotomy and sequently reperfusion to establish myocardial ischemia/reperfusion no reflow models.Sham operation group weren’t underwent occlusion of coronary artery. On the28th day after operation, cardiac function in all surviving rats were evaluated by echocardiography.Rats were sacrificed.Picrosirius red staining plus light microscopy was used to quantitive analysize thickness of left ventricular free wall in infracted region(left ventricular free wall for sham group, LVWT),septum(SPD) and ratio of SPT/LVWT, myocardial across area in septum(MAAS)and collagen volume fraction in non-infarcted and infracted region(left ventricular free wall for sham group).Results::For acute experiments,after120minutes for reperfosion,there were no statistical differences in ARR/LV among control group,adenosine group and nicorandil group (P>0.05).A markedly reduced NA/AAR and ANR/AAR observed in nicorandil group and adenosine group,and the differences were significant compared with the control group(P<0.01).This illustrated that nicorandil and adenosine reduced size of myocardial infarct,area of no reflow and improved myocardial perfusion. The result showed that the serum myocardial enzyme of adenosine group and nicorandil group was lower than control group.The differences were significant (P<0.01), especially in CK and CK-MB, nicorandil group was better than adenosine group. It displayed that nicorandil could improve the degree of myocardial damage, which was better than adenosine.For chronic experiments,after28days for reperfosion and than evaluating cardiac structure and function,cardiac ultrasound showed that the ejection fraction (EF) of rat in nicorandil group was significantly increased and the differences were significant compared with the control group(P<0.05), while end-diastolic volume(EDV) was decreased significantly (P<0.01).It showed that nicorandil could improve ejection fraction of left ventricle and reduce end-diastolic volume. Meanwhile,rats were sacrificed. There was myocardial fibrosis,Fibroblast proliferation and collagen deposition,in the area of myocardial infarction with control group,resulted in ventricular remodeling.The statistical differences were significant in reducing the degree of fibrosis compared with the control group(P<0.01).This displayed that nicorandil and adenosine both reduced the extent of myocardial fibrosis Improved ventricular remodeling pathological stage of myocardial infarction.Conclusions:This work of the study concluded that nicorandil reduced size of myocardial infarct,area of no reflow and improved myocardial perfusion and ejection fraction,decreased end-diastolic volume,as well as reduced the extent of myocardial fibrosis improved ventricular remodeling pathological stage of myocardial infarction in the SD rats animal model of myocardial ischemia reperfusion.The mechanism and effect between nicorandil and adenosine were resemble.The novelty of the research is embodied as follows:1. We compared characteristics of nicorandil and adenosine in no-reflow phenomenon and ventricular remodeling after acute myocardial ischemia-reperfusion and explored the advantage of nicorandil,in order to provide scientific basis for nicorandil of clinical treatment.2. Nicorandil could effectively improve the ventricular function in myocardial ischemia-reperfusion, as well as in protecting myocardial cells and in reducing myocardial damage, which was better than adenosine. |
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