| Objective To assess the effect of Tongxinluo on cytokines, vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction.Methods Forty mini-swine were divided into five groups randomly, sham group, control group, low dose (0.1g/kg), medium dose (0.2g/kg) and high dose (0.4g/kg) group of Tongxinluo, which were administered two hours before reperfusion. Animals except in sham group were subjected to 1.5 hour of coronary occlusion followed by 3 hours of reperfusion. Serum contents of P-selectin, intercellular adhesion molecule 1(ICAM-1), vascular cell adhesion molecule 1(VCAM-1), interleukin 6 (IL-6) and interleukin 10(IL-10) were evaluated at baseline,1.5 hour of AMI and 3 hours of reperfusion; Content of VE-cadherin,β-catenin,matrix metalloproteinase (MMP)-2 and 9 in the myocardium were evaluated; no-reflow area were evaluated with myocardial contrast echocardiography(MCE)at 1.5 hour of AMI and 3 hours of reperfusion.Results(1)Compared with that of control group,high dose of Tongxinluo could reduce serum content of P-selectin,ICAM-1 at 1.5 hour of AMI(all p<0.05),and P-selectin,ICAM-1,VCAM-1, IL-6 at 3 hours of reperfusion significantly(all p<0.05), accompanied by IL-10 increasing(p<0.05):(2)Compared with that of normal myocardium,content of VE-cadherin andβ-catenin decreased in reperfusion and no-reflow myocardium while MMP-2 and 9 increased significantly(all p<0.05):(3)Compared with that of control group,high dose of Tongxinluo could increase content of VE-cadherin in both reperfus ion and no-reflow myocardium significantly,(22.2±3.2)％vs (32.0±3.9)％and (14.5±2.8)％vs (28.3±2.2)％respectively,β-catenin, (20.5±3.5)％vs (27.3±2.9)％and (13.3±2.1)％vs (20.6±2.4)％,while reduce MMP-2, (48.3±4.1)％vs (29.4±3.5)％and (57.3±4.3)％vs (38.2±4.0)％respectively, MMP-9, (55.6±4.0)％vs (34.3±3.5)％and (62.4±4.8)％vs (44.4±4.1)％,all p<0.05:(4)Compared with that of control group,high dose of Tongxinluo could reduce both no-reflow area,(6.6±1.7)cm2 vs (4.7±1.5)cm2,p<0.05,and percentage, (90.8±3.75)％vs (71.4±4.09)％,p<0.05,at 3 hours of reperfusion significantly, which evaluated with myocardial contrast echocardiography(MCE).Conclusion High dose of Tongxinluo could effectively reduce serum content of adhesional and inflammatory cytokines, while effectively maintain the integrity of vascular endothelium, and attenuate no-ref low area in early reperfusion of acute myocardial infarction. Objective To evaluate the protective effect of Tongxinluo in myocardial no-reflow after emergency percutaneous interventional therapy(PCI) of acute myocardial infarction.Methods 211 patients (female 14%, age 58±16) enrolled in this randomized, double-blind, placebo controlled, multicenters clinical trial. Patients were taken Tongxinluo (n=108) or placebo (n=111) 2.08g before emergency PCI with asprin (300mg) and clopidogrel (300mg) together, then were continued to take six months with 1.04g tid until the end of the trial. The elevation of ST segment in electrocardiogram was measured at baseline, 1h, 2h,6h,12h and 24h after the reperfusion; the SPECT was taken in day 7 and day 180 after the reperfusion, tracer accumulation was scored with four-point scoring system to evaluate no-reflow and infarction area. Results There's no significant difference of sex, age, onset time, Killip degree, elevation of ST segment and TIMI flow between two groups at baseline (all p>0.05), either of medication such as aspirin, clopidogrel, statin,β-blocker or ACEI (all p>0.05). Compared with placebo, Tongxinluo facilitated the restoration of ST segment at 6h,12h and 24h after reperfusion significantly,-0.22mV±0.18mV vs -0.18mV±0.16mV,-0.24mV±0.18mV vs -0.18mV±0.15mV and -0.27mV±0.16mV vs-0.20mV±0.16mV, p value was 0.0394,0.0158 and 0.0021 separately; and incidence of myocardial no-reflow was also reduced significantly (34.3% vs 54.1%, p =0.0031) at 24h after reperfusion which evaluated with electrocardiogram. Compared with placebo, Tongxinluo improved severity score of SPECT in day 7 and day 180 after reperfusion significantly,0.61±0.40 vs 0.76±0.42 and 0.51±0.42 vs 0.66±0.43, p value was 0.0109 and 0.0115 separately.Conclusion Tongxinluo attenuated myocardial no-reflow and reduced infarction area after emergency PCI for acute myocardial infarction.
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