刘琪,蔡新勇,詹宇亮,黄笑,刘松涛,邹鹏涛,陈淮钢,罗睿,邵靓,洪浪

• 1:江西省人民医院(南昌医学院第一附属医院)心内科
• 2:南昌大学医学院

摘要(Abstract)：

目的 探讨冠状动脉内应用不同剂量重组人尿激酶原对急性ST段抬高型心肌梗死（STEMI）行急诊经皮冠状动脉介入治疗（PCI）术后心肌灌注的影响。方法 本研究包括江西省人民医院和宜春市人民医院2018年5月至2022年10月420例行急诊PCI的STEMI患者，在急诊PCI术中患者采用不透明信封进行随机化分组，按照2:1:1的比例根据纳入和排除标准，共纳入379例患者分为生理盐水组201例、10mg重组人尿激酶原组99例、20mg重组人尿激酶原组79例。主要终点是术后90min罪犯血管导联ST段回落率（STR），次要终点是术后心肌梗死溶栓治疗试验（TIMI）血流计数帧数（CTFC）、术后TIMI血流分级、主要不良心血管事件（MACE）发生率；安全性评价是住院期间出血事件，以TIMI出血分级为标准。结果 3组患者的术后90 min的STR≥70%发生率分别是31.0%、47.7%、57.1%(P=0.001)；进行两两比较后，生理盐水组和10 mg重组人尿激酶原组、20 mg重组人尿激酶原组相比STR≥70%发生率的差异均有统计学意义（P=0.010、P=0.002），且生理盐水组术后导联ST段不回落发生率高于20 mg重组人尿激酶原组（21.8%比7.1%,P=0.046）。3组患者的术后CTFC、术后TIMI血流分级、MACE比较，差异均无统计学意义（均P>0.05）。在安全性事件上，20 mg重组人尿激酶原组发生了更多的出血事件，主要在轻微出血事件方面（P=0.002）。结论 冠状动脉内应用重组人尿激酶原可显著改善患者的心肌灌注，但随着重组人尿激酶原剂量的增加，术后轻微出血事件发生率也随之增加。

关键词(KeyWords)： 急性ST段抬高型心肌梗死;经皮冠状动脉介入治疗;重组人尿激酶原;微循环功能障碍

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 刘琪,蔡新勇,詹宇亮,黄笑,刘松涛,邹鹏涛,陈淮钢,罗睿,邵靓,洪浪

参考文献(References)：

• [1] Ibanez B,James S,Agewall S,et al.2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation:the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology(ESC)[J].Eur Heart J,2018,39(2):119-177.DOI:10.1093/eurheartj/ehx3 93.
• [2]de Waha S,Patel MR,Granger CB,et al.Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction:an individual patient data pooled analysis from seven randomized trials[J].Eur Heart J,2017,38(47):3502-3510.DOI:10.1093/eurheartj/ehx414.
• [3] Cuculi F,De Maria GL,Meier P,et al.Impact of microvascular obstruction on the assessment of coronaw flow reserve,index of microcirculatory resistance,and fractional flow reserve after STsegment elevation myocardial infarction[J].J Am Coll Cardiol,2014,64(18):1894-1904.DOI:10.1016/j.jacc.2014.07.987.
• [4]Henriques JP,Zijlstra F,Ottervanger JP,et al.Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction[J].Eur Heart J,2002,23(14):1112-1117.DOI:10.1053/euhj.2001.3035.
• [5] Jolly SS,James S,Dzavik V,et al.Thrombus aspiration in ST-segment-elevation myocardial infarction:an individual patient meta-analysis:thrombectomy trialists collaboration[J].Circulation,2017,135(2):143-152.DOI:10.1161/CIRCUL ATIONAHA.116.025371.
• [6]Carrick D,Oldroyd KG,McEntegart M,et al.A randomized trial of deferred stenting versus immediate stenting to prevent no-or slow-reflow in acute ST-segment elevation myocardial infarction(DEFER-STEMI)[J].J Am Coll Cardiol,2014,63(20):2088-2098.DOI:10.1016/j.jacc.2014.02.530.
• [7]Niu X,Zhang J,Bai M,et al.Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction:a network Meta-analysis[J].BMC Cardiovasc Disord,2018,18(1):3.DOI:10.1186/s12872-017-0722-z.
• [8]Kaddoura R,Mohamed Ibrahim MI,Al-Badriyeh D,et al.Intracoronary pharmacological therapy versus aspiration thrombectomy in STEMI(IPAT-STEMI):a systematic review and meta-analysis of randomized trials[J].PLoS One,2022,17(5):e0263270.DOI:10.1371/journal.pone.0263270.
• [9]Credo RB,Burke SE.Fibrinolytic mechanism,biochemistry,and preclinical pharmacology of recombinant prourokinase[J].J Vasc Interv Radiol,1995,6(6 Pt 2 Suppl):8S-18S.DOI:10.1016/s1051-0443(95)71242-8.
• [10]Gibson CM,Cannon CP,Daley WL,et al.TIMI frame count:a quantitative method of assessing coronary artery flow[J].Circulation,1996,93(5):879-88.DOI:10.1161/01.cir.93.5.879.
• [11]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.ST段抬高型心肌梗死患者急诊PCI微循环保护策略中国专家共识[J].中华心血管病杂志,2022,50(3):221-230.DOI:10.3760/cma.j.cn112148-20211112-00987.
• [12]Davies MJ,Thomas A.Thrombosis and acute coronaryartery lesions in sudden cardiac ischemic death[J].N Engl J Med,1984,310(18):1137-1140.DOI:10.1056/NEJM198405033101801.
• [13]郝伟,赵晨,胡思宁,等.急性ST段抬高型心肌梗死患者直接经皮冠状动脉介入治疗术后无复流现象的最新研究进展[J].中国介入心脏病学杂志,2023,31(5):380-386.DOI:10.3969/j.issn.1004-8812.2023.05.010.
• [14] Mastoris I,Giustino G,Sartori S,et al.Efficacy and safety of routine thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention:an updated systematic review and Meta-analysis of randomized controlled trials[J].Catheter Cardiovasc Intern,2016,87(4):650-660.DOI:10.1002/ccd.26152.
• [15] Touboul C,Angoulvant D,Mewton N,et al.Ischaemic postconditioning reduces infarct size:systematic review and Meta-analysis of randomized controlled trials[J].Arch Cardiovasc Dis,2015,108(1):39-49.DOI:10.1016/j.acvd.2014.08.004.
• [16]Cassese S,Belle L,Ndrepepa G,et al.Deferred vs.immediate stenting in primary percutaneous coronary intervention:a collaborative meta-analysis of randomized trials with cardiac magnetic resonance imaging data[J].Can J Cardiol,2018,34(12):1573-1580.DOI:10.1016/j.cjca.2018.07.480.
• [17]Erlinge D,Gotberg M,Lang I,et al.Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction.The CHILL-MI trial:a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction[J].J Am Coll Cardiol,2014,63(18):1857-1865.DOI:10.1016/j.jacc.2013.12.027.
• [18] Burzotta F,Trani C,Romagnoli E,et al.Manual thrombusaspiration improves myocardial reperfusion:the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty(REMEDIA)trial[J].J Am Coll Cardiol,2005,46(2):371-376.DOI:10.1016/j.jacc.2005.04.057.
• [19] De Luca G,Dudek D,Sardella G,et al.Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction:a Meta-analysis of randomized trials[J].Eur Heart J,2008,29(24):3002-3010.DOI:10.1093/eurheartj/ehn389.
• [20] Jolly SS,Cairns JA,Yusuf S,et al.Randomized trial of primary PCI with or without routine manual thrombectomy[J].N Engl J Med,2015,372(15):1389-1398.DOI:10.1056/NEJMoa1415098.
• [21]Lagerqvist B,Fr?bert O,Olivecrona GK,et al.Outcomes 1 year after thrombus aspiration for myocardial infarction[J].N Engl J Med,2014,371(12):1111-1120.DOI:10.1056/NEJMoa1405707.
• [22]Dominguez AC,Bittl JA,El-Hayek G,et al.Meta-analysis of randomized controlled trials comparing percutaneous coronaryintervention with aspiration thrombectomy vs.Conventional percutaneous coronary intervention during ST-segment elevation myocardial infarction[J].Catheter Cardiovasc Interv,2016,87(7):1203-1210.DOI:10.1002/ccd.26352.
• [23]耿涛,宋志远,刘娟,等.经抽吸导管冠状动脉内注射重组人尿激酶原的安全性和有效性[J].中国介入心脏病学杂志,2021,29(8):447-453.DOI:10.3969/j.issn.1004-8812.2021.08.005.
• [24] Stone GW,Maehara A,Witzenbichler B,et al.Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction:the INFUSE-AMI randomized trial[J].JAMA,2012,307(17):1817-1826.DOI:10.1001/jama.2012.421.
• [25]Mitchel JF,Fram DB,Palme DF 2nd,et al.Enhanced intracoronary thrombolysis with urokinase using a novel,local drug delivery system.In vitro,in vivo,and clinical studies[J].Circulation,1995,91(3):785-793.DOI:10.1161/01.cir.91.3.785.
• [26]Burke SE,Lubbers NL,Nelson RA,et al.Profile of recombinant pro-urokinase given by mtraarterial versus intravenous routes of administration in a canine thrombosis model[J].Thromb Haemost,1999,81(2):301-305.
• [27]Boscarelli D,Vaquerizo B,Miranda-Guardiola F,et al.Intracoronary thrombolysis in patients with ST-segment elevation myocardial infarction presenting with massive intraluminal thrombus and failed aspiration[J].Eur Heart J Acute Cardiovasc Care,2014,3(3):229-236.DOI:10.1177/204887261452700.8
• [28]高胜男,刘国强.重组人尿激酶原与阿替普酶治疗急性ST段抬高型心肌梗死的成本效果分析[J].中国新药杂志,2017,26(14):1725-1728.
• [29]Liu Y,Yang Y,Li Y,et al.Comparison of efficacy and safety of recombinant human prourokinase and alteplase in the treatment of STEMI and analysis of influencing factors of efficacy[J].Evid Based Complement Alternat Med,2021,2021:6702965.DOI:10.1155/2021/6702965.
• [30]Rommel KP,Baum A,Mende M,et al.Prognostic significance and relationship of worst lead residual ST segmentelevation with myocardial damage assessed by cardiovascular MRI in myocardial infarction[J].Heart,2014,100(16):1257-1263.DOI:10.1136/heartjnl-2013-305462.
• [31] Reinstadler SJ,Baum A,Rommel KP,et al.ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction[J].Heart,2015,101(22):1819-1825.DOI:10.1136/heartjnl-2015-307876.
• [32]Cao M,Wang Z,Meng X,et al.Effects of intracoronary low-dose prourokinase administration on ST-segment elevation in patients with myocardial infarction and a high thrombus burden:a randomized controlled trial[J].J Int Med Res,2022,50(12):3000605221139723.DOI:10.1177/03000605221139723.
• [33]Yin XS,Huang YW,Li ZP,et al.Efficacy and safety of intracoronary pro-urokinase injection during percutaneous coronary intervention in treating ST elevation myocardial infarction patients:a systematic review and Meta-analysis of randomized controlled trials[J].Eur Rev Med Pharmacol Sci,2022,26(16):5802-5813.DOI:10.26355/eurrev 202208 29518.
• [34] Mathews SI,Parikh SA,Wu W,et al.Sustained mechanical aspiration thrombectomy for high thrombus burden coronary vessel occlusion:the multicenter CHEETAH study[J].Circ Cardiovasc Interv,2023,16(2):e012433.DOI:10.1161/CIRCINTERVENTIONS.122.012433.
• [35]Zhao S,Qi G,Tian W,et al.Effect of intracoronary nitroprusside in preventing no reflow phenomenon during primary percutaneous coronary intervention:a Meta-analysis[J].J Interv Cardiol,2014,27(4):356-364.DOI:10.1111/joic.12133.
• [36]Nallamothu B,Fox KA,Kennelly BM,et al.Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention.The Global Registry of Acute Coronary Events[J].Heart,2007,93(12):1552-1555.DOI:10.1136/hrt.2006.112847.