The Research Of Carvedilol As A Protective Agent Against Myocardial Ischemia-Reperfusion Injury

Objective: To determine the changes on the expression level of the leucocyte adhesion molecules in acute myocardial infarction (AMI) patients after percutaneous transluminal coronary angioplasty(PTCA) and Stent Implantation; To explore the effects of Carvedilol on adhesion molecules, myocardium infarction area and left ventricle fuction ; To explore the mechanism of Carvedilol on prevention of myocardial ischemia-reperfusion injury.Methods: Fifty patients were randomly divided into three groups, including Control group(n=10), Metoprolol group(n=20) and Carvedilol group(n=20). The expression level of CD11b, CD18, ICAM-1, and L-selectin were assessed at three time points (operated immediately, seven days later, three months later) in all groups by indirect immunofluorescence flow cytometry. Ultrasonic cardiogram was used to meature the left ventricular internal diameter at end-diastole (LVEDD), left ventricular internal diameter at end-systole (LVESD), and left ventricular ejection fraction (LVEF) in all groups at 7th day and 3th month. Double-head detector SPECT was used to detect the change of myocardium infarction area by (99m)~Tc-MIBI myocardial perfusion imaging at 7th day and 3th month.Results: In Control group, the numbers of CD11b and CD18 positive cell were decreased gradually, but the numbers of ICAM-1 and L-selectin positive cell were increased at 7th day.In Carvedilol group, the numbers of CD11b positive cell were significantly lower than Metoprolol group and Control group [(53.90±26.46)% vs(74.30±16.57)%, P＜0.01; (53.90±26.46)% vs(78.69±5.55)%, P＜0.01]; Compared with Control group, the percentage of CD18 positive cell in Metoprolol group and Carvedilol group were markedly decreased [(66.97±9.12)%vs(73.00±6.74)%, P＜0.05; (63.18±17.93)% vs(73.00±6.74)%, P＜0.05]; the percentage of ICAM-1 positive cell in Carvedilol group was lower significantly than that of the others [(7.29±7.52)% vs (12.86±9.67)%, P＜0.05; (7.29±7.52)% vs (14.35±10.09) %, P＜0.05];the significant statistic difference of the percentage of L-selectin positive cell existed between Carvedilol group and the others [(21.78±12.66)% vs (38.96±13.67)%, P＜0.01; (21.78±12.66)% vs (45.50±20.30)%, P＜0.01].Three months later, there was a significant difference of the numbers of CD11b positive cell between Carvedilol group and the others [(45.92±18.26)% vs (61.14±27.84)%, P＜0.05; (45.92±18.26)% vs (73.63±24.33)%, P＜0.01]; there was a significant difference of the numbers of CD18 positive cell between Carvedilol group and Control groups [(52.74±23.30)% vs (70.02±21.59)%, P＜0.05]; there was a significant difference of the numbers of ICAM-1 positive cell between Carvedilol group and Control groups [(5.62±4.36)% vs (6.8±3.72)%, P＜0.05]; the significant statistic difference of the percentage of L-selectin positive cell existed between Carvedilol group and the others [(8.86±3.57)% vs (15.62±7.41)%, P＜0.01; (8.86±3.57)% vs (12.64±5.34)%, P＜0.05].Follow-up period ranged from seven days to three months, no obvious change of myocardium infarction area was found (P＞0.05)Seven days later, there was no difference of LVEDD,LVESD and LVEF in three groups (P＞0.05) .Three months later, there was no difference of LVEDD in three groups (P＞0.05) ,but there were significant differences of the LVESD and LVEF between Carvedilol group and the others (P＜0.05) ; there was no difference of LVESD and LVEF between Metoprolol group and Control group (P＞0.05).Conclusion: The expression of the adhesion molecules downregulated significantly in peripheral blood after Carvedilol was administered, and its effect was generally better than Metoprolol. During the follow-up period, no evidence of Carvedilol and Metoprolol decreased the myocardium infarction size was found. The LVESD was significantly decreased and the LVEF was markly increased after Carvedilol was administered. The function of left ventricle could be improved greatly by Carvedilol, and its effect on the aspect was significantly better than Metoprolol. All in all, Carvedilol plays an important role in the prevention of myocardial ischemia-reperfusion injury.