冠状动脉无复流现象的防治

冠状动脉无复流现象的防治冠状动脉无复流现象的防治武警部队心脏研究所武警部队心脏研究所武警部队心血管介入中心武警部队心血管介入中心 罗建平罗建平武警总医院心血管内科武警总医院心血管内科病人资料病人资料n毛某，男性，78岁，n糖尿病8年，高血压病，高脂血症，吸烟20余年，1年前戒除n主因发作性剑突下疼痛4天，于2007年09月18日由门诊以“冠心病 急性心肌梗死”收入科。nECG：V1-V5导联ST段抬高0.2mv。n肌钙蛋白升高。CAGCAG球囊扩张前冠脉内给予硝酸甘球囊扩张前冠脉内给予硝酸甘油油200ug，欣维宁，欣维宁10ml 2.5*15mm球囊扩张球囊扩张球囊扩张后球囊扩张后植入支架植入支架3.0*24mm植入后造影植入后造影no-reflow先后冠脉给予欣维宁再先后冠脉给予欣维宁再10ml、硝酸甘油、硝酸甘油400ug，异搏定，异搏定400ug后后 近端植入支架近端植入支架3.5*14mm植入后造影植入后造影no-reflow再先后冠脉给予欣维宁再先后冠脉给予欣维宁10ml、硝酸甘油、硝酸甘油500ug，异搏定，异搏定600ug后后 一、无复流概述一、无复流概述n 无复流现象无复流现象(no-reflow)(no-reflow)是指闭塞是指闭塞的心外膜冠状动脉再通后，心肌组的心外膜冠状动脉再通后，心肌组织无灌注的现象。冠状动脉造影表织无灌注的现象。冠状动脉造影表现为血流明显减慢现为血流明显减慢(血流血流=50%)或或ST段抬高指数增加段抬高指数增加(=30%)，对判断微血管灌注或无复流均有较高准确对判断微血管灌注或无复流均有较高准确性性(81%)。3、心电图、心电图n经皮冠状动脉介入治疗后原病变部位无夹层、经皮冠状动脉介入治疗后原病变部位无夹层、痉挛或阻塞而冠状动脉血流小于心肌梗死溶痉挛或阻塞而冠状动脉血流小于心肌梗死溶栓治疗临床试验栓治疗临床试验(TIMI)II(TIMI)II级或心肌灌注级或心肌灌注(TMP)(TMP)血流分级血流分级0-20-2级，可以判定无复流。对于冠级，可以判定无复流。对于冠状动脉血流状动脉血流TIMI IIITIMI III级的病例，一部分表现级的病例，一部分表现为缓慢血流，另一部分为快血流，缓慢血流为缓慢血流，另一部分为快血流，缓慢血流患者经超声、核素检查后仍可检出无复流病患者经超声、核素检查后仍可检出无复流病例，提示例，提示TIMITIMI血流分级在判定无复流方面存血流分级在判定无复流方面存在局限性。在局限性。4、冠状动脉造影血流分级、冠状动脉造影血流分级n在传统的在传统的TIMI血流分级法基础上用校正的血流分级法基础上用校正的TIMI帧数来评估微循环血流。这是一种较帧数来评估微循环血流。这是一种较精确的识别技术，较传统的精确的识别技术，较传统的TIMI分级客观、分级客观、定量、可重复、敏感。造影剂到达指定的定量、可重复、敏感。造影剂到达指定的冠状动脉远端所需的血管造影帧数越多，冠状动脉远端所需的血管造影帧数越多，血流速度越慢，无复流存在的可能越大。血流速度越慢，无复流存在的可能越大。5、校正的心肌梗死溶栓治疗临床、校正的心肌梗死溶栓治疗临床试验帧数试验帧数(CTFC)n采用多普勒血流导丝，进行血管内超声检查，采用多普勒血流导丝，进行血管内超声检查，测定时相性和平均冠状动脉血流速度；测定绝测定时相性和平均冠状动脉血流速度；测定绝对冠状动脉血流储备对冠状动脉血流储备(CFR)指数，若显示冠状指数，若显示冠状动脉血流储备指数下降，收缩期顺向血流速度动脉血流储备指数下降，收缩期顺向血流速度下降，异常收缩早期逆向血流，舒张期血流速下降，异常收缩早期逆向血流，舒张期血流速度迅速下降均提示无复流现象。收缩早期逆向度迅速下降均提示无复流现象。收缩早期逆向血流是具有敏感性和特异性的评估无复流的指血流是具有敏感性和特异性的评估无复流的指标。标。6、冠状动脉内多普勒血流、冠状动脉内多普勒血流 7、超声心肌声学造影、超声心肌声学造影(MCE)n 将声处理的造影物质将声处理的造影物质(如氟丙烷白蛋白如氟丙烷白蛋白)，其中，其中含高能微泡，从冠状动脉或静脉途径注入，然含高能微泡，从冠状动脉或静脉途径注入，然后做心肌超声检查，受累区无复流灌注反应或后做心肌超声检查，受累区无复流灌注反应或心肌内气泡反常持续存在提示无复流现象。心肌内气泡反常持续存在提示无复流现象。n目前由于声学造影剂的改进，二次谐波成像技目前由于声学造影剂的改进，二次谐波成像技术的应用和心肌声学造影分析方法的进步，心术的应用和心肌声学造影分析方法的进步，心肌声学造影被认为是目前评估活体冠状动脉微肌声学造影被认为是目前评估活体冠状动脉微循环异常的最有效方法之一。循环异常的最有效方法之一。8、冠状动脉内压力测定、冠状动脉内压力测定n应用压力导丝测量靶动脉的压力阶差，应用压力导丝测量靶动脉的压力阶差，并计算心肌血流储备分数并计算心肌血流储备分数(FFRmyo)。当有微循环病变存在时，血流储备分数当有微循环病变存在时，血流储备分数值会升高，此时还应当结合冠状动脉内值会升高，此时还应当结合冠状动脉内血流储备分数进行判断。如果血流储备血流储备分数进行判断。如果血流储备分数值较高而冠状动脉血流储备值低，分数值较高而冠状动脉血流储备值低，说明有微血管功能障碍存在。说明有微血管功能障碍存在。9、其他方法、其他方法n放射性核素运动心肌灌注显像、正电放射性核素运动心肌灌注显像、正电子发射断层和对比增强磁共振显像法，子发射断层和对比增强磁共振显像法，都可用于诊断无复流。都可用于诊断无复流。四、无复流的危险因素四、无复流的危险因素nPCI术后是否发生无复流可根据临床特术后是否发生无复流可根据临床特点、冠状动脉造影及冠状动脉内超声结点、冠状动脉造影及冠状动脉内超声结果进行初步判断。果进行初步判断。n研究发现，研究发现，SVG PCI时，血栓形成、时，血栓形成、ACS、退化的静脉移植物、溃疡是发生、退化的静脉移植物、溃疡是发生低或无复流的低或无复流的4个独立危险因素，发生个独立危险因素，发生SNR的危险分别为：低危的危险分别为：低危(1%-10%)=3个危险因素。个危险因素。nAMI PCIAMI PCI时，时，CAGCAG见高负见高负荷的血栓形成是发生无荷的血栓形成是发生无复流现象的独立预测因复流现象的独立预测因素，表现为：素，表现为：IRAIRA完全闭完全闭塞处呈切面残端、阻塞塞处呈切面残端、阻塞近端血栓近端血栓5mm5mm、浮动血、浮动血栓存在、阻塞远端造影栓存在、阻塞远端造影剂持续淤滞、参考管腔剂持续淤滞、参考管腔直径直径(RLD)=4mm(RLD)=4mm、IIII型型病变病变(IRA(IRA不完全阻塞性不完全阻塞性血栓长度超过血栓长度超过RLD3RLD3倍倍)。nIVUSIVUS见到的有脂质池样图象的大血管也见到的有脂质池样图象的大血管也处于发生无复流的高危险。处于发生无复流的高危险。n相反，早期再灌注相反，早期再灌注240min=2TIMI=2级、锥形阻塞，为不发生级、锥形阻塞，为不发生无复流的独立预测因素。无复流的独立预测因素。五、无复流的防治五、无复流的防治预防预防n药物药物n远端保护远端保护/血栓抽吸装置（主要用于桥血血栓抽吸装置（主要用于桥血管管PCIPCI和和AMIAMI直接直接PCIPCI）n直接支架植入直接支架植入n准分子激光消栓准分子激光消栓药物药物PCIPCI术前或术中冠状动脉内或外周静脉给药术前或术中冠状动脉内或外周静脉给药 硝酸甘油硝酸甘油（Nitroglycerin）腺苷腺苷（Adenosine）尼可地尔尼可地尔(K(KATPATP通道开放剂通道开放剂)（Nicorandil）维拉帕米维拉帕米（Verapamil）地尔硫卓地尔硫卓（Diltiazem）GP IIb/IIIaGP IIb/IIIa受体拮抗剂受体拮抗剂（GP IIb/IIIa receptor antagonist）等等均可减少无复流现象的发生。均可减少无复流现象的发生。维拉帕米维拉帕米Early Administration of Intracoronary Verapamil Improves Myocardial Perfusion During Percutaneous Coronary Interventions for Acute Myocardial InfarctionnAMI 直接PCI前冠脉内给予维拉帕米改善心肌灌注(CHEST 2005;128:25932598)目的：目的：To evaluate the effects of the administration of intracoronary verapamil before the occurrence of no reflow during direct PCI.n50 patients ready to undergo direct PCI within 12 h from the onset of AMInIntracoronary verapamil was administered immediately prior to balloon inflationnHad not received intracoronary calcium-channel blockers were enrolled as control subjects.(CHEST 2005;128:25932598)(CHEST 2005;128:25932598)TMPG：TIMI myocardial perfusion grade尼可地尔尼可地尔nEffects of Intravenous Nicorandil Before Reperfusion for Acute Myocardial Infarction in Patients With Stress HyperglycemianAMI并应激性高血糖病人再灌注治疗前并应激性高血糖病人再灌注治疗前静脉注射尼可地尔的疗效静脉注射尼可地尔的疗效Diabetes Care 29:202206,2006nMETHODS：This study consisted of 158 consecutive first AMI patients with stress hyperglycemia who underwent PCI within 24 h from the onset.They were randomly assigned to receive 12 mg of nicorandil(n=81)or a placebo(n=77)intravenously just before reperfusion.nStress hyperglycemia was defined as a blood glucose level 10 mmol/l(180 mg/dl).Diabetes Care 29:202206,2006（P=0.032）（P=0.027）（P=0.032）Diabetes Care 29:202206,2006尼可地尔不同给药途径的疗效尼可地尔不同给药途径的疗效nImpact of Nicorandil to Prevent Reperfusion Injury in Patients With Acute Myocardial InfarctionnSigmart Multicenter Angioplasty Revascularization Trial(SMART)Circ J 2006;70:1099 1104)n90 个个AMI起病起病6小时内的住院病人，小时内的住院病人，PCI前前TIMI血流血流0-1级。级。n随机分为随机分为A、B、C 3组组，nA组：尼可地尔组：尼可地尔 0.5 mg/次，次，PCI前和后前和后1-2次冠次冠脉注射脉注射(总量原则上总量原则上1-2 mg)。nB组：将尼可地尔配成组：将尼可地尔配成1 mg/ml.先静脉推注先静脉推注4 mg，然后，然后6ml/h静脉输注，加上静脉输注，加上A组方案冠脉组方案冠脉内给药。内给药。nC组：无药组组：无药组Circ J 2006;70:1099 1104)Circ J 2006;70:1099 1104)Fig 1.Primary endpoint.*p 50%50%并并为心绞痛罪犯血管的患者，随机分为为心绞痛罪犯血管的患者，随机分为PCIPCI术中术中使用使用 Guardwire Plus Guardwire Plus 的远端球囊阻塞的远端球囊阻塞/血栓血栓抽吸装置组（抽吸装置组（N=406 N=406）和传统）和传统0.014 inch0.014 inch导丝导丝组组 （N=395 N=395）n主要终点：主要终点：3030天内死亡、心肌梗死、急诊搭桥天内死亡、心肌梗死、急诊搭桥或靶病变再血管成形术的联合终点。或靶病变再血管成形术的联合终点。Circulation.2002;105:1285-1290.)Circulation.2002;105:1285-1290.)(P=0.004)（P=0.008)（P=0.02)nThe Distal Protection During Primary Percutaneous Coronary Intervention Alleviates the Adverse Effects of Large Thrombus Burden on Myocardial Reperfusionn远端保护对大血栓负荷直接远端保护对大血栓负荷直接PCI心肌再灌注心肌再灌注的影响的影响Circ J 2006;70:232 238n88 consecutive patients undergoing DP during primary PCI within 24 h from the onset of AMI were enrolled in the study(DP group).n81 consecutive patients undergoing primary PCI without using the DP device for AMI during the preceding 1 year(control group).Circ J 2006;70:232 238nThe GuardWire Plus(Medtronic)consists of a 0.014-inch guidewire incorporating a central inflation lumen to which an elastomeric balloon(3.06.0 mm in diameter)Circ J 2006;70:232 238Circ J 2006;70:232 238P0.05Circ J 2006;70:232 238Circ J 2006;70:232 238P0.05nLimitations of using a GuardWire temporary occlusion and aspiration system in patients with acute myocardial infarction:multicenter investigation of coronary artery protection with a distal occlusion device in acute myocardial infarction(MICADO).J-Invasive-Cardiol.2007 Mar;19(3):132-8 MICADOnThe study was conducted as a prospective，randomized，multicenter trial.nThis study evaluated the efficacy of distal protection with the GuardWire distal protection device in PCI at the time of AMI revascularization.nPatients with AMI within 24 hours from onset were randomized into either PCI combined with a GuardWire，or PCI without distal protection.nThe primary endpoints were TIMI perfusion grade(TMP)and no incidence of reflow.nSecondary endpoints were major cardiac events(MACE)during 6-month follow up.J-Invasive-Cardiol.2007 Mar;19(3):132-8 J-Invasive-Cardiol.2007 Mar;19(3):132-8（p=0.054）MACE was observed in similar incidences between the two groups after 6-month follow upX-Sizer机械血栓抽吸装置机械血栓抽吸装置nIncidence,predictors,and outcomes of device failure of X-sizer thrombectomy:Real-world experience of 200 cases in 5 yearsAm Heart J 2007;153:14.e13-14.e19.Am Heart J 2007;153:14.e13-14.e19.Am Heart J 2007;153:14.e13-14.e19.Am Heart J 2007;153:14.e13-14.e19.直接支架植入直接支架植入A Randomized Comparison of Direct Stenting With Conventional Stent Implantation in Selected Patients With Acute Myocardial InfarctionAMI直接支架植入和传统支架植入的随机对照直接支架植入和传统支架植入的随机对照研究研究J Am Coll Cardiol 2002;39:1521nrandomized,single-center trialn206 were allocated to direct stent implantation(n=102)or stent implantation after balloon pre-dilation(n=104)J Am Coll Cardiol 2002;39:1521J Am Coll Cardiol 2002;39:1521J Am Coll Cardiol 2002;39:1521两组住院期间的临床结果两组住院期间的临床结果准分子激光消栓准分子激光消栓nExcimer laser thrombus elimination for prevention of distal embolization and no-reflow in patients with acute ST elevation myocardial infarctionn Results from the randomized Laser AMI studyn27 consecutive patients with ST-segment elevation AMI(aged 57.89.2 years)were randomized either to balloon angioplasty and stent implantation alone(n=13)or adjunct ELCA(n=14).International Journal of Cardiology 116(2007)2026nELCA was feasible and safe in all cases.No procedure-associated complications were observed.International Journal of Cardiology 116(2007)2026P0.05International Journal of Cardiology 116(2007)2026International Journal of Cardiology 116(2007)2026治疗治疗硝酸甘油硝酸甘油（Nitroglycerin）腺苷腺苷（Adenosine）尼可地尔尼可地尔(K(KATPATP通道开放剂通道开放剂)（Nicorandil）维拉帕米维拉帕米（Verapamil）地尔硫卓地尔硫卓（Diltiazem）硝普钠硝普钠（Sodium Nitroprusside）乌拉地尔乌拉地尔（Urapidil）GP IIb/IIIaGP IIb/IIIa受体拮抗剂受体拮抗剂（GP IIb/IIIa receptor antagonist）Intracoronary Verapamil for Reversal of No-Reflow During Coronary Angioplasty for Acute Myocardial Infarctionn冠脉内给予维拉帕米逆转冠脉内给予维拉帕米逆转AMI冠状动脉成形术冠状动脉成形术中无复流中无复流Cathet Cardiovasc Intervent 002;57:444451.na consecutive series of 212 direct or rescue PTCAs for AMI，a TIMI flow grade 3 was observed in 23 patients(10.8%)nTen of the 23 patients had received GP IIb/IIIa antagonists before PTCACathet Cardiovasc Intervent 002;57:444451.A：LAD闭塞，闭塞，B：球囊扩张后：球囊扩张后TIMI2级血流，级血流，C：支架植入后：支架植入后无血流，无血流，D：沿导丝送入灌注导管至支架远端，注入维拉帕米：沿导丝送入灌注导管至支架远端，注入维拉帕米1mg，E：保留灌注导管造影：保留灌注导管造影TIMI3级，级，F：15MIN后造影后造影Cathet Cardiovasc Intervent 002;57:444451.Individual changes of TFC in 23 patients with no-reflow after intracoronary verapamil.The significant change of group mean standard deviation is also shown(P 0.001).Cathet Cardiovasc Intervent 002;57:444451.Cathet Cardiovasc Intervent 002;57:444451.腺甘和钙桔抗剂的实验对比研究腺甘和钙桔抗剂的实验对比研究Cardiovasc Drugs Ther(2006)20:167175结扎区域(LA)，无复流区域(ANR)，坏死区域(NA)Histopathological 组织病理学