BACKGROUND:The early reperfusion of the infarct-related artery in acute myocardial infarction (AMI) may significantly improve the symptoms and prognosis of patients.However,reperfusion is also followed by ischemia-reperfusion injury and there are no very effective ways to manage this severe problem at present.OBJECTIVE:To evaluate the protective effects of intracoronary adenosine infusion on myocardium in patients with AMI during percutaneous coronary intervention(PCI).DESIGN:Double-blinded and randomized controlled study.SETTING:First Hospital of Hebei Medical University and Third Hospital of Shijiazhuang City.PARTICIPANTS:The clinical triel was performed in 50 eligible patients at the Department of Cardiology,the First Hospital of Hebei Medical University and the Third Hospital of Shijiazhuang City from December 2004 to April 2006.Patients were eligible if they were age 30 years or older and admitted with ST-segment elevation myocardial infarction (STEMI).The diagnosis of STEMI was based on episodes of chest pain persisting at least 30 minutes but no longer than 12 hours and proving unresponsive to nitrates,electrocardiogram (ECG) ST-segment elevation of at least 2 contiguous ECG leads,and 2-fold creatine kinase (CK) elevation above the maximum peak in the normal range.The physicians obtained written informed consent from each patient.The patients were randomly assigned into two groups:those who received intra-coronary adenosine (23 patients) and those who received placebo (saline,27 patients).There were no significant differences between two groups in general condition,characteristics of coronary angiograms and intervention procedure(P＞0.05).METHODS:After the patients were admitted in hospital,general emergence managements were given.All patients received 300 mg aspirin and 300 mg clopidogrel. While the patients remained stable,the left and right coronary arteriography was done before the balloon was inflated.10 mL saline (control group) or adenosine (300 μg+10 mL saline) was immediately given by intracoronary injection within one minute.Then the stenting was performed.Coronary flow of the infarct-related artery (IRA) was assessed by the method of thrombolysis in myocardial infarction (TIMI) grading.MAIN OUTCOME MEASURES:①The peaks of serum levels of cardiac biomarkers were assessed every 4 hours in the first day of admission and then every day up to discharge.②The 12-lead ECG was done 1 hour before coronary angiography and after PCI,the sum of ST-segment resolution (STR) was calculated.③The left ventricular ejection fraction (LVEF) was calculated and measured by echocardiogram on the 3rd day and the fourth week after PCI in modified Simpson's method.RESULTS:All of 50 patients with AMI were involved in the final analysis.①Cardiac biomarkers and sum of STR:The peak levels of serum CK,CK-MB and cardiac troponin Ⅰ (cTnI) in adenosine group were significantly lower than those in control group (t=2.31,z=2.83,2.22;P＜0.05).Sum of STR in one hour after PCI of adenosine group were significantly higher than those in control group (z=2.10,P＜0.05).The lower level of the markers in adenosine group showed the mild myocardial injury.The infarcted patients with more rapid ST-segment resolution in adenosine group meant the better recovery in the electrocardiogram.②Left ventricular function:LVEF at the fourth week of PCI (both adenosine and control group) were better than those on the third day (t=1.45,2.30;P＜0.01).LVEF in adenosine group were significantly higher than control group on the fourth week after PCI.TIMI flow:TIMI 3 flow in the two groups was 22 patients for control group and 19 patients for adenosine group.There was no significant difference between the two groups(P＞0.05).③Side-effect:Four(17.39%) patients in adenosine group and 1(3.70%) patient in control group developed significant sinus bradycardia requiring pacing.However,the incidence of bradycardia requiring pacing was not significantly different between the two groups(Fisher exact,P=0.129).CONCLUSIONS:Intracoronary adenosine infusion during PCI significantly alleviated ischemia-reperfusion injury and improved the left ventricular function in AMI.Intracoronary adenosine infusion in patients with AMI during PCI was safe and feasible.%背景:急性心肌梗死早期血管再通治疗可显著改善患者的症状及预后,但同时容易引起缺血再灌注损伤,对此尚缺乏有效的治疗手段.目的:观察经皮冠状动脉支架置入治疗急性心肌梗死中,冠状动脉内应用腺苷的心肌保护作用.设计:双盲随机对照实验.单位:河北医科大学第一医院及石家庄市第三医院.对象:选择2004-12/2006-04在河北医科大学第一医院和石家庄市第三医院心内科住院的年龄≥30岁的急性心肌梗死患者50例.均符合急性心肌梗死的诊断标准,即持续性胸痛≥30 min且不长于12 h、硝酸酯类药物不能缓解;体表心电图相邻两个导联ST段抬高＞0.1 mV,并且肌酸激酶升高＞正常高值的2倍.纳入患者或家属签属治疗方案知情同意书.采用双盲随机方法将患者分为腺苷组(n=23)和对照组(n=27),两组患者一般状况、冠脉造影及支架置入治疗特征比较,差异无显著性意义(P＞0.05).方法:患者入院后即给予常规的急性心肌梗死一般抢救及监护措施,同时应用阿司匹林300 mg和氯吡格雷300 mg 1次顿服并在进行急诊经皮冠状动脉支架置入治疗术前准备后直接入导管室行选择性冠状动脉造影术,术后行经皮冠状动脉支架置人治疗.先以球囊预扩张开通梗塞相关动脉,腺苷组患者即刻予以腺苷300μg+10 mL生理盐水,对照组患者给予生理盐水10 mL.持续1 min通过指引导管进行冠状动脉内注射完毕,再予以支架治疗.术毕按心肌梗死溶栓治疗临床试验血流分级对梗死相关动脉进行再通后血流评价.主要观察指标:①入院后第1天每4 h、术后第2天至出院每天检测心脏生物标记物.②术前、术后1 h进行12导联心电图检查,分析ST段抬高总和回落百分比.③分别于经皮冠状动脉支架置入治疗后的第3天及第4周应用改良Simpson氏法计算左心室射血分数,观察患者的左心室功能.结果:纳入的50例急性心肌梗死患者全部进入结果分析.①两组患者心脏标记物峰值及ST段抬高总和回落百分比分析比较:腺苷组患者心脏标记物肌酸激酶及其同功酶、心脏肌钙蛋白I峰值明显低于对照组,差异有显著性意义(t=2.31,z=2.83,2.22,P＜0.05);腺苷组ST段抬高总和回落百分比高于对照组,差异有显著性意义(z=2.10,P＜0.05).腺苷组心脏标记物峰值较低说明心肌损伤轻于对照组,ST段抬高总和回落百分比的增加说明腺苷组患者心电图ST段恢复较快.②两组患者心功能比较:术后4周时左心室射学分数均增加,与术后3 d比较,差异有显著性意义(t=1.45,2.30,P＜0.01),且腺苷组的改善更明显.对照组和腺苷组患者心肌梗死溶栓治疗临床试验血流分级3级者分别为22和19例,两组比较,差异无显著性意义(P＞0.05).③两组患者不良反应发生情况比较:腺苷组4例(17.3%)、对照组1例(3.7%)出现有意义的窦性心动过缓而可见起搏心律,两组比较,差异无显著性意义(Fisher确切概率P=0.129).结论:急性心肌梗死直接经皮冠状动脉支架置入治疗中,冠状动脉内注射腺苷可以明显缓解急性心肌梗死血管开通背景下发生的缺血再灌注损伤,有益于改善左心功能,且安全性较好.
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