【作者】 李静；

【导师】 刘俊；

【作者基本信息】 大连医科大学 ， 内科学， 2013， 硕士

【摘要】 研究背景：大规模临床试验已证实急性ST段抬高型心肌梗死心肌微循环障碍（慢血流或无复流）的机制之一是缺血再灌注损伤。而氧化应激是缺血再灌注损伤发生、发展的主要机制。氧化应激有多种相关检测指标，如超氧化物歧化酶（SOD）、血清氧化型低密度脂蛋白（ox-LDL）、丙二醛（MDA）等。随着我国急性心肌梗死发病率的上升以及冠心病介入治疗数量的增加，心肌微循环障碍导致的不良心血管事件受到人们越来越多的关注，从而加强了对预防和改善无复流或慢血流药物的研究。改善心肌微循环障碍的传统药物有维拉帕米[1]、腺苷[2-3]、硝普钠[4]、阿昔单抗等，均可部分逆转无复流，但由于增加出血风险、负性肌力作用等限制了临床应用，因此寻找安全、有效的替代药物成为重要研究课题。近几年来，人们对Rho/ROCK途径在心血管疾病方面的研究逐步深入，目前已有多种Rho激酶抑制剂问世。而法舒地尔是目前临床试验中应用最多且证据充分的Rho激酶抑制剂。法舒地尔能够通过减轻氧化应激缓解缺血再灌注损伤，但法舒地尔能否改善急性ST段抬高型心肌梗死心肌微循环障碍（无复流或慢血流）有待证实。目的：研究法舒地尔对急性ST段抬高型心肌梗死患者直接PCI术中慢血流或无复流现象的治疗效果。方法：研究对象取自2011年1月至2012年12月连续住院的患者，因STEMI（2010年ACC/AHA治疗指南定义）接受直接PCI术，且术中出现无复流或慢血流现象者。随机分为A、B两组，A组为法舒地尔组（将法舒地尔以4mg/20ml/3min通过微导管直接注射到冠脉血管内）；B组为维拉帕米组（将维拉帕米以0.5mg/20ml/3min通过微导管直接注射到冠脉血管内）。观察A、B两组的临床特征、冠状动脉病变分布特点、心肌呈色分级（MBG）、术后24小时内心电图ST段的变化程度、注药前以及注药后15分钟SOD的水平、安全性评估。结果1.入选86例患者，其中A组45例，平均年龄67.06±12.9岁，男：女（例）25:20；B组41例，平均年龄65.87±9.53岁，男：女（例）25:16。两组患者年龄、性别比例、冠心病的危险因素、冠状动脉病变的分布特点、介入手术时间均无统计学差异（P﹥0.05）。2. A组与B组比较心肌呈色分级明显改善（2.10±0.11对1.50±0.13P=0.003），术后24小时心电图ST段回落大于70%的比率增加（68%对45%，P=0.004）。3. A组与B组注药前SOD水平均无显著性差异（P=0.45）。注药15分钟后A组SOD水平由375.31±55.07pg/ml升至524.93±57.67pg/ml（P﹤0.01），B组SOD水平由382.61±55.28pg/ml升至529.21±56.30pg/ml（P﹤0.01）。A组SOD水平的上升幅度高于B组，有统计学意义（P﹤0.05）。4.安全性评估：两组注射药物之前的平均动脉压分别为A组92.24±24.36mmHg、B组88.92±19.85mmHg，P=0.536；心率分别为A组67.35±14.35次/分、B组70.55±16.44次/分，P=0.12。A组注射药物3分钟内出现一过性血压轻度减低，心率无明显变化，注射终止时血压与注射前相比无明显波动；B组注射药物后则迅速出现低血压并持续于较低水平，需要使用多巴胺的比率明显增加，A组比B组为34.67%比62.36%，P﹤0.05。A组注射药物后心率未产生明显影响，而B组则迅速出现心率减慢，应用临时起搏的比率显著增加，A组比B组为23.67%比74.65%，P﹤0.05。结论STEMI直接PCI术中出现无复流或慢血流患者冠脉内注射药物后缺血再灌注损伤均较前改善。注射不同药物的两组进行比较显示，法舒地尔的治疗效果优于维拉帕米。法舒地尔作为新的血管扩张药物可以用于改善STEMI直接PCI术中的无复流或慢血流现象，改善心肌微循环障碍。更多还原

【Abstract】 Background: Large clinical trials have confirmed that in acute ST-segmentelevation myocardial infarction dysfunction, ischemia reperfusion injury is one of themechanisms of myocardial microcirculation (slow flow or no reflow), and oxidativestress is the main factor of the occurrence and development. Oxidative stress has avariety of related indicators, such as superoxide dismutase (SOD), serum type oxidizedlow density lipoprotein (ox-LDL), malondialdehyde (MDA), etc.With the risingindicence of acute myocardial infarction and the increasing cases of interventionaltreatment of coronary heart disease in our country, adverse cardiovascular events causedby myocardial microcirculation disorder have been brought into focus.A large body ofresearch has been carrzed out the myocardial microcirculation. Traditional drugs such asverapamil[1], adenosine[2-3], sodium nitroprusside[4]and abciximab can partially reverse no-reflow, but the increased risk of bleeding and negative inotropic effect have limited theclinical application. Therefore,it is an important research topic to look for safe andeffective alternative medicine.Recent studies have provided a deeper insight into therole of the Rho/ROCK pathway in cardiovascular disease.Now,several Rho kinaseinhibitors have been development.Among them fasudil is currently the most commonyused with sufficient evidence in clinical trials.Fasudil can inhibit oxidative stress andthus relieve ischemia-reperfusion injury.But whether fasudil can improve themyocardial microcirculation of ASTEMI patients (no reflow or slow blood flow) duringPCI in remains to be confirmed.Objective:To eyaluate the effect of fasudil on the microcirculation dysfunction (noreflow or slow blood flow)during direct PCI for ASTEMI patients.Methods: The subjects were selected from the hospitalized patients with STEMI(diagnosed according to the ACC/AHA2010guidelines).They all received directpercutaneous coronary internetion and had no reflow or slow blood flow phenomenonduring the procedure from January2011to December2012.They were randomized into groups,Group A and Group B. The subjects in Group A received fasudil (injectedthrough the micro catheter into the coronary arteries at4mg/20ml/3min). The patients inGroup B received verapamil(injected through the micro catheter into the coronaryarteries at0.5mg/20ml/3min). The clinical features, distribution of coronary arterylesions,myocardial blush grades （MBG）,ST-segmen（tSTR,＞70%）24hour after thepercutaneous coronary internetion, the levels of superoxide dismutase before and isminutes after drug infusion and the safety indicators were observed in the two groups.Results:1.86patients are selected, Group A:45cases, mean age67.06±12.9years,male/female ratio25:20；Group B:41cases, mean age65.87±9.53years, male/femaleratio25:16. There was no difference in the follow aspects on the baseline between twogroups: Age, sex ratio, risk factors for coronary heart disease, distribution of coronaryartery lesions frame the severity of the coronary artery lesions and the time of theinterventional procedure, P﹥0.05.2. MBG grade in Group A improved sighficantly compared with that in Group B(2.10±0.11vs.1.50±0.13, P=0.003); the percentage of24h-STR in Group A also exceedsthat in Group B(68%vs.45%, P=0.004).3. There was no difference in the level of superoxide dismutase before druginfusion between the two groups,(P=0.45).15min after drug infusion,the level of SODin Group A rised from375.31±55.07to524.93±57.67pg/ml, P﹤0.01And in Group B itincreased from382.61±55.28pg/ml to529.21±56.30pg/ml,(P﹤0.01). The increase inSOD in Group A was higher than that in Group B, and the difference was statisticallydifferent(P﹤0.05)4. Safety assessment: the mean arterial pressure of the two groups before druginjection were92.24±24.36mmHg and88.92±19.85mmHg,(P=0.536); The meanheart rate was67.35±14.35beats/minute in Group A and it was70.55±16.44beats/minute in Group B,(P=0.12).With in3minutes after drug injection,transient mildblood pressure coourred in Group A.Hear Rate did not vary significantly.And there isno significant difference in BP berfe after drug injection.In Group B,low blood pressureoccurred rapidly after drug injection and persisted at a relatively low lever.Thepercentage of subjects who needed dopamine were significantly higher than that inGroup A(34.67%vs62.36%. P﹤0.05).Inaddition,subjects in Group B had siower heartrate immediately,and the percentage of temporary pacemaker were remarkable higher than that in Group A(23.67%vs74.65%, P﹤0.05).Conclusion: The condition of no-reflow or slow-flow during direct PCI forSTEMI patients was improved after intra coronary drug injection.Compared betweenthe two groups,the efficacy of fasudil is superior to that of verapamil.Fasudil,as a novelvasodilation, can be used to treat the no-reflow or slow-flow in PCI for STEMIpatients,and relieve myocardial microcirculation dysfunction.更多还原