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冠状动脉内注射尿激酶原在ST段抬高型心肌梗死患者急诊经皮冠状动脉介入术中的应用效果研究

来源:搜集整理   日期:2021-12-21   点击数:

  摘    要:背景经皮冠状动脉介入术(PCI)是ST段抬高型心肌梗死(STEMI)的有效治疗手段,大多数患者术后能够恢复正常血供,少数患者心肌再灌注效果较难达到预期,冠状动脉内溶栓是救治此类患者的有效途径。尿激酶原在急性栓塞性疾病的救治中发挥积极作用,但关于其在STEMI患者PCI中的应用效果仍存在争议。目的 观察冠状动脉内注射尿激酶原在STEMI患者急诊PCI中的应用效果。方法 选取2019年1月至2020年1月北京航天总医院接受急诊PCI的STEMI患者86例为研究对象。依据患者治疗方法的不同,将其分为对照组、观察组,各43例。观察组术中在冠状动脉内注射尿激酶原进行治疗,对照组进行常规治疗。比较两组治疗前和治疗后12、24、36 h心肌损伤标志物[肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)],治疗前和治疗后心肌组织灌注分级,治疗前和治疗后12、24、36 h心肌梗死面积,不良心血管事件发生率。结果 治疗方法与时间在CK-MB、cTnI上存在交互作用(P <0.05);治疗方法、时间在CK-MB、cTnI上主效应显著(P <0.05)。观察组患者治疗后12、24、36 h CKMB、c TnI低于对照组(P <0.05)。对照组、观察组患者治疗后12、24、36 h CK-MB、cTnI分别高于本组治疗前,治疗后24、36 h CK-MB、cTnI分别低于本组治疗后12 h,治疗后36 h CK-MB、cTnI分别低于本组治疗后24 h(P <0.05)。观察组患者治疗后心肌灌注分级优于对照组(P <0.05)。治疗方法与时间在心肌梗死面积上存在交互作用(P <0.05);治疗方法、时间在心肌梗死面积上主效应显著(P <0.05)。观察组患者治疗后12、24、36 h心肌梗死面积小于对照组(P <0.05)。对照组、观察组患者治疗后12、24、36 h心肌梗死面积分别小于本组治疗前,治疗后24、36 h心肌梗死面积分别小于本组治疗后12 h,治疗后36 h心肌梗死面积分别小于本组治疗后24 h(P <0.05)。观察组患者不良心血管事件发生率低于对照组(P <0.05)。结论 冠状动脉内注射尿激酶原在STEMI患者PCI中有明确的应用效果,其可减轻患者心肌损伤程度、改善血流灌注、缩小心肌梗死面积和降低不良心血管事件发生风险。
  
  关键词:ST段抬高型心肌梗死 尿激酶原 冠状动脉 经皮冠状动脉介入治疗 治疗结果
  
  Effect of Intracoronary Injection of Prourokinase in Emergency Percutaneous Coronary Intervention of Patients with ST Segment Elevation Myocardial Infarction
  
  WANG Jin WANG Rong LU Hui
  
  No.2 Department of Cardiology, Beijing Aerospace General Hospital;
  
  Abstract:Background Percutaneous coronary intervention(PCI) is an effective treatment for ST segment elevation myocardial infarction(STEMI). Most patients can restore normal blood supply after operation, and a few patients are difficult to achieve the expected myocardial reperfusion effect. Intracoronary thrombolysis is an effective treatment for such patients.Prourokinase plays an active role in the treatment of acute embolic diseases, but its effect in PCI in STEMI patients is still controversial. Objective To observe the effect of intracoronary injection of prourokinase in emergency PCI of patients with STEMI. Methods A total of 86 patients with STEMI who underwent emergency PCI in Beijing Aerospace General Hospital from January 2019 to January 2020 were selected as the research subjects. They were divided into control group and observation group according to the treatment method, with 43 cases in each group. Patients in the observation group were treated with intracoronary injection of prourokinase during PCI, while patients in the control group were given conventional treatments. The myocardial injury markers [creatine kinase isoenzyme(CK-MB), cardiac troponin I(cTnI) ] before treatment and at 12, 24 and 36 h after treatment,myocardial tissue perfusion classification before and after treatment, myocardial infarction area before treatment and at 12, 24 and 36 h after treatment, and the incidence of adverse cardiovascular events were compared between the two groups. Results There was interaction effect between treatment method and time on CK-MB and cTnI(P < 0.05); the main effects of treatment method and time on CK-MB and cTnI were significant(P < 0.05). CK-MB and cTnI in the observation group were significantly lower than those in the control group at 12, 24 and 36 h after treatment(P < 0.05). In the control group and observation group, CKMB and cTnI at 12, 24 and 36 h after treatment were higher than those before treatment, CK-MB and cTnI at 24 and 36 h after treatment were lower than those at 12 h after treatment, CK-MB and cTnI at 36 h after treatment were lower than those at 24 h after treatment, respectively(P < 0.05). The myocardial tissue perfusion classification of the observation group was better than that of the control group(P < 0.05). There was interaction effect between treatment method and time on myocardial infarction area(P < 0.05); the main effects of treatment method and time on myocardial infarction area were significant(P < 0.05). The myocardial infarction area of the observation group was smaller than that of the control group at 12, 24 and 36 h after treatment(P < 0.05). In the control group and observation group, the myocardial infarction area at 12, 24 and 36 h after treatment was smaller than that before treatment, the myocardial infarction area at 24 and 36 h after treatment was smaller than that at 12 h after treatment, and the myocardial infarction area at 36 h after treatment was smaller than that at 24 h after treatment, respectively(P < 0.05). The incidence of adverse cardiovascular events in the observation group was lower than that in the control group(P < 0.05). Conclusion Intracoronary injection of prourokinase has a clear application effect in PCI of STEMI patients. It can reduce the degree of myocardial injury, improve blood perfusion, reduce the area of myocardial infarction, and reduce the risk of adverse cardiovascular events.
  
  Keyword:ST segment elevation myocardial infarction; Prourokinase; Coronary arteries; Percutaneous coronary intervention; Treatment outcome;
  
  ST段抬高型心肌梗死(ST segment elevation myocardial infarction,STEMI)指典型缺血性胸痛持续时间不短于20 min,血清心肌坏死标志物水平持续增高,心电图有典型ST段抬高的急性心肌梗死。近年来随着我国老龄化的加重,STEMI发病率逐年递增,是目前全球范围内的一个公共卫生问题[1]。冠状动脉内不稳定斑块破裂是STEMI的病理基础,斑块破裂不仅会引起微血栓,且易堵塞冠状动脉,致患者发生心绞痛、心肌坏死等,给患者生命健康造成严重威胁[2]。经皮冠状动脉介入术(percutaneous coronary intervention,PCI)仍是当前STEMI患者的有效治疗手段,但有研究发现,部分患者PCI围术期出现无复流或慢血流现象,影响心肌灌注效果,不仅引起心肌二次损伤,而且明显增加患者病死率,已成为临床关注的焦点[3-4]。心肌灌注不良与术中斑块或血栓脱落所致微循环堵塞密切相关,国内外学者研究发现,冠状动脉内小剂量溶栓药可有效改善患者心肌灌注和心功能[5-7]。但现阶段关于冠状动脉内注射尿激酶原对接受急诊PCI的STEMI患者心肌灌注、梗死面积和预后等的影响尚无明确定论。本研究旨在分析冠状动脉内注射尿激酶原在STEMI患者急诊PCI中的应用效果,以期为接受急诊PCI的STEMI患者的临床治疗提供参考。
  
  1 对象与方法
  
  1.1 研究对象
  
  选取2019年1月至2020年1月北京航天总医院接受急诊PCI的STEMI患者86例为研究对象。纳入标准:(1)符合中华医学会心血管病学分会制定的《急性ST段抬高型心肌梗死诊断和治疗指南》[8]中的STEMI诊断标准;(2)症状发作到入院时间<12 h;(3)临床资料完整。排除标准:(1)肝、肾功能不全者;(2)伴有慢性感染性疾病者;(3)伴有自身免疫性疾病或恶性肿瘤者;(4)对造影剂或尿激酶原过敏者;(5)伴有冠状动脉主干急性闭塞者;(6)近1个月内接受外科手术者;(7)伴有活动性出血、凝血功能异常者。依据患者治疗方法的不同,将其分为对照组、观察组,各43例。对照组中男24例,女19例;年龄48~68岁,平均(56.1±2.2)岁;病变血管:左前降支25例,左回旋支13例,右冠状动脉5例;病变血管支数:1支26例,2支12例,3支5例。观察组中男25例,女18例;年龄49~69岁,平均(56.0±2.3)岁;病变血管:左前降支27例,左回旋支12例,右冠状动脉4例;病变血管支数:1支25例,2支13例,3支5例。两组患者性别(χ2=0.047,P=0.828)、年龄(t=0.206,P=0.837)、病变血管(χ2=0.228,P=0.892)、病变血管支数(χ2=0.060,P=0.971)比较,差异无统计学意义。所有患者签署了知情同意书,本研究经北京航天总医院医学伦理委员会批准同意。
  
  1.2治疗方法
  
  患者均参照《急性ST段抬高型心肌梗死诊断和治疗指南》[8]中的相关治疗规范进行常规对症治疗。观察组术中在冠状动脉内注射尿激酶原进行治疗:冠状动脉造影穿刺路径为桡动脉,采用Seldinger's技术进行穿刺,予以100 U/kg普通肝素进行抗凝,沿引导钢丝置入球囊,对闭塞处进行扩张(扩张压力为5 atm),撤出球囊,球囊膜上穿刺2个微孔,将有孔球囊置于病变处,通过球囊尾端缓慢注射重组尿激酶原(上海天士力药业有限公司生产,批号201804123)溶液(10 mg重组尿激酶原溶于10 ml 0.9%氯化钠溶液中),5 min内推注完毕。对照组进行常规治疗,采用同样方法注射10 ml 0.9%氯化钠溶液,5 min内推注完毕。而后两组患者均接受支架置入术(采用美敦力公司生产的Endeavor Resolute支架)。术后两组患者均口服阿司匹林片100 mg、1次/d,氯吡格雷片75 mg、1次/d。并根据患者病情,合理使用他汀类药物、血管紧张素转换酶抑制剂、β-受体阻滞剂、硝酸酯类药物。
  
  1.3 观察指标
  
  (1)心肌损伤标志物。分别于治疗前和治疗后12、24、36 h采用免疫定量分析仪(QMT8000型)检测两组患者血清心肌损伤标志物,包括肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)、心肌肌钙蛋白I(cardiac troponin I,cTnI)。(2)心肌组织灌注分级。分别于治疗前和治疗后采用心肌组织灌注分级[9]评估患者心肌灌注情况,其中梗死动脉供血区心肌不存在对比剂染色为0级;梗死动脉供血区心肌对比剂染色较为缓慢且色淡,较难排空为1级;梗死动脉供血区心肌对比剂染色较快且可排空,但稍延迟为2级;梗死动脉供血区心肌对比剂染色较快且可迅速排空为3级。(3)心肌梗死面积。分别于治疗前和治疗后12、24、36 h对患者进行心电图检查,记录S波及Q波等,采用Selvester QRS公式计算积分值,1积分表示心肌梗死面积为3%,根据积分计算心肌梗死面积。(4)不良心血管事件发生率。治疗后1个月,统计患者不良心血管事件(包括心肌梗死、心绞痛、心源性休克、心律失常、心力衰竭)发生率。
  
  1.4 统计学方法
  
  采用SPSS 20.0统计学软件进行数据分析。计数资料以相对数表示,组间比较采用χ2检验,等级资料比较采用秩和检验;计量资料以表示,组间比较采用两独立样本t检验,重复测量资料比较采用双因素重复测量方差分析。以P<0.05为差异有统计学意义。
  
  2 结果
  
  2.1 两组患者不同时间心肌损伤标志物比较
  
  治疗方法与时间在CK-MB、c TnI上存在交互作用(P<0.05);治疗方法、时间在CK-MB、cTnI上主效应显著(P<0.05)。观察组患者治疗后12、24、36 h CK-MB、cTnI低于对照组,差异有统计学意义(P<0.05)。对照组、观察组患者治疗后12、24、36 h CK-MB、cTnI分别高于本组治疗前,治疗后24、36 h CK-MB、cTnI分别低于本组治疗后12 h,治疗后36 h CK-MB、cTnI分别低于本组治疗后24 h,差异有统计学意义(P<0.05),见表1。
  
  2.2 两组患者治疗前后心肌组织灌注分级比较
  
  两组患者治疗前心肌组织灌注分级比较,差异无统计学意义(P>0.05);观察组患者治疗后心肌灌注分级优于对照组,差异有统计学意义(P<0.05),见表2。
  
  2.3 两组患者不同时间心肌梗死面积比较
  
  治疗方法与时间在心肌梗死面积上存在交互作用(P<0.05);治疗方法、时间在心肌梗死面积上主效应显著(P<0.05)。观察组患者治疗后12、24、36 h心肌梗死面积小于对照组,差异有统计学意义(P<0.05)。对照组、观察组患者治疗后12、24、36 h心肌梗死面积分别小于本组治疗前,治疗后24、36 h心肌梗死面积分别小于本组治疗后12 h,治疗后36 h心肌梗死面积分别小于本组治疗后24 h,差异有统计学意义(P<0.05),见表3。
  
  2.4 两组患者不良心血管事件发生率比较
  
  对照组患者治疗后1个月发生心绞痛4例、心律失常2例、心力衰竭2例、心肌梗死1例、心源性休克1例,不良心血管事件发生率为23.3%(10/43);观察组患者治疗后1个月发生心律失常2例、心绞痛1例,不良心血管事件发生率为7.0%(3/43)。观察组患者不良心血管事件发生率低于对照组,差异有统计学意义(χ2=4.441,P=0.035)。
  
  3 讨论
  
  据统计,STEMI患者PCI后慢血流现象发生率为19%~30%[10]。慢血流指心外膜闭塞冠状动脉,经溶栓或急诊介入治疗后正常开通,但因微血管水平血流较难全部恢复,导致缺血心肌组织无法有效再灌注的现象,是引发STEMI患者PCI后心功能不全、恶性心律失常及心室内血栓形成等不良心血管事件的重要原因[11-12]。STEMI患者PCI后发生慢血流现象是其不良预后的独立预测因素,其发生的原因有:PCI操作过程中引起的斑块破裂或血栓脱落,导致冠状动脉远端心肌水平循环障碍,心肌灌注水平降低[13-14]。研究证实,尿激酶原在STEMI患者PCI中有明确的应用效果,其属于尿激酶的前体物质,可激活血栓纤维表面的纤溶酶原,但对游离纤溶酶原无明显活性,有出血风险低、安全性高等优点[15-16]。但现阶段关于冠状动脉内注射尿激酶原对接受急诊PCI的STEMI患者心肌灌注、梗死面积和预后等的影响尚无明确定论。本研究旨在进一步分析冠状动脉内注射尿激酶原在STEMI患者急诊PCI中的应用效果。
  
  表1 两组患者不同时间心肌损伤标志物比较
  
  表2 两组患者治疗前后心肌组织灌注分级比较[n(%)]
  
  表3 两组患者不同时间心肌梗死面积比较
  
  血清CK-MB、cTnI可反映心肌损伤程度,患者发生急性心肌梗死后机体内CK-MB、cTnI会释放入血,因此血液中CK-MB、cTnI表达水平对STEMI发作后血栓溶解效果有一定评估作用[17]。心肌组织灌注分级可评估患者心肌灌注情况,分级越高表明患者心肌水平的有效灌注越高[18]。而心肌梗死面积不仅预示溶栓治疗疗效,且可评估患者的预后。本研究结果显示,观察组患者治疗后12、24、36 h CK-MB、cTnI低于对照组;提示STEMI患者急诊PCI中冠状动脉内注射尿激酶原可降低CK-MB、cTnI,有效减轻心肌损伤程度,这与尿激酶原可有效降低冠状动脉血栓负荷、改善微循环、最大限度保护心肌细胞有关[19]。本研究结果还显示,观察组患者治疗后心肌灌注分级优于对照组;观察组患者治疗后12、24、36 h心肌梗死面积小于对照组;观察组患者不良心血管事件发生率低于对照组;提示STEMI患者急诊PCI中冠状动脉内注射尿激酶原可明显改善患者心肌灌注情况,有效减小心肌梗死面积,并降低STEMI患者PCI后不良心血管事件发生风险。分析原因为,观察组术中冠状动脉内注射尿激酶原后,药物可随时与血栓接触并发挥溶栓作用,当球囊扩张或支架植入后,药物可随微栓塞一起流向远端并达到溶栓效果,这不仅可有效改善患者心肌血液循环,而且可明显恢复患者心肌灌注,减小心肌梗死面积,改善患者预后[20]。
  
  综上所述,冠状动脉内注射尿激酶原在STEMI患者PCI中有明确的应用效果,其可减轻患者心肌损伤程度、改善血流灌注、缩小心肌梗死面积和降低不良心血管事件发生风险。但本研究存在样本量较小、随访时间短等不足,今后还需要大样本量的多中心研究进一步验证本研究结论。
  
  作者贡献:王进进行文章的构思与设计、研究的实施与可行性分析、数据整理、结果的分析与解释,撰写论文,负责文章的质量控制及审校,并对文章整体负责、监督管理;王进、王蓉、陆蕙进行数据收集;王进、王蓉进行统计学处理、论文的修订。
  
  本文无利益冲突。
  
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