PCI术后心肌缺血损伤机制与治疗的研究进展

经皮冠状动脉介入治疗术(percutaneous coronary artery intervention,PCI术)是冠心病患者血运重建的重要手段,但临床观察显示PCI术后经出现慢血流、无复流,再灌注心律失常及心肌酶学的升高,直接影响患者的预后。因此,减少PCI术后的心肌损伤是改善冠心病患者经PCI术后预后的关键。目前研究认为PCI术后心肌缺血再灌注损伤的发病机制主要与心肌再灌注时与氧自由基生成增多、细胞内Ca2+超载、心肌细胞能量代谢障碍、微血管损伤、粒细胞浸润以及心肌细胞的凋亡等多方面的作用有关,而PCI术后心肌损伤的保护治疗方面主要有药物与器械两方面。本文就PCI术后心肌缺血再灌注损伤的机制及保护治疗的研究进展作一综述。     

替罗非班对NSTEMI患者PCI术后心肌再灌注影响的心肌声学造影评价

目的:探讨替罗非班对非ST段抬高型心肌梗死(NSTEMI)患者冠状动脉介入治疗(PCI)术后心肌再灌注的改善效果。方法:收取2012年4月至2015年4月在我院接受PCI治疗的NSTEMI患者78例作为研究对象,按照使用药物的不同将其分为观察组(n=38)及对照组(n=40)。对照组患者给予阿司匹林+氯吡格雷+肝素等常规治疗,观察组在此基础上加用替罗非班。使用心肌声学造影(MCE)评价两组患者心肌再灌注的情况。结果:PCI术前,两组患者A、β、Aβ、CK-MB及c Tn I比较差异均无统计学意义(P0.05);治疗后,两组各指标均上升,且观察组β及Aβ显著高于对照组,CK-MB及c Tn I低于对照组(P0.05)。观察组心脏不良事件发生率为2.63%,对照组为5.00%,两组安全性比较差异无统计学意义(P0.05)。结论:替罗非班可显著改善NSTEMI患者PCI术后心肌再灌注,且安全性高。     

维拉帕米对急性前壁心肌梗死行急诊PCI术患者再灌注室性心律失常的影响

目的:探讨经指引导管早期应用维拉帕米对急性前壁心肌梗死行急诊经皮冠状动脉介入治疗术(Percutaneous Coronary Intervention,PCI)患者再灌注室性心律失常的影响。方法:采用单中心、随机对照、前瞻性研究方法。选取2014年5月-2016年11月诊断为急性前壁心肌梗死并于我院行急诊PCI的患者,共纳入162例患者,按随机方法(随机数字表)分成2组,其中治疗组82例,对照组80例。治疗组患者在首次球囊扩张后早期经指引导管内给予维拉帕米(200μg),对照组患者则给予生理盐水。观察再灌注后室性心律失常发生率,PCI术后冠脉血流情况,心肌梗死相关血清指标(CK-MB,cTn I)的峰值,住院期间发生的主要不良心血管事件(MACE)。结果:维拉帕米治疗组患者再灌注心律室性失常及无复流的发生率显著低于生理盐水对照组(P0.05);维拉帕米治疗组患者cTnI和CK-MB峰值分别为(46.63±13.77)μg/L和(139.87±35.45)U/L,生理盐水组cTnI和CK-MB峰值为(54.36±12.59)μg/L和(158.34±40.18)U/L,两组比较,P均0.01。MACE事件两组间未见有统计学差异。结论:急性前壁心肌梗死患者急诊PCI术前经导管早期给予维拉帕米不但可显著减少无复流现象,还可显著减少再灌注后室性心律失常的发生,住院期间MACE事件的发生率无显著性差异。     

冠状动脉介入治疗对冠心病患者Caspase-3,9 水平的影响

目的:通过对冠心病患者经皮冠状动脉介入治疗(PCI)前后血清Caspase-3,9水平变化的观察,探讨冠状动脉介入治疗对冠心病患者血清Caspase-3,9水平的影响。方法:冠状动脉介入组(PCI组)30例和单纯造影组(CAG组)29例,在术前0.5h,术后3h,术后6h,术后12h,术后24h,术后48h分别测定血清Caspase-3,9水平。结果:CAG组术前与术后的血清Caspase-3,9水平差异均无统计学意义,PCI组术后3h、6h的Caspase-3水平较术前0.5h均有降低趋势,差异均有统计学意义(P<0.05),PCI组术后48h的Caspase-9水平与术后3h、6h相比均有升高趋势,差异均有统计学意义(P<0.05)。结论:PCI术后狭窄或闭塞的冠状动脉血管重新恢复血供,血清中Caspase-3,9水平在PCI术后先降低后又逐渐升高,提示再灌注后可出现细胞的凋亡程度加重,血清中Caspase-3,9的水平可作为心肌再灌注损伤后细胞凋亡程度的评估指标并可作为诊断临床症状不典型的再灌注损伤的一个指标。PCI术可有效改善心肌血供,减少因术前缺血缺氧造成的细胞凋亡,但PCI术后再灌注损伤可进一步加重细胞凋亡。     

急性心肌梗死行PCI患者炎症因子的检测及其与预后的关系

目的:探讨急性心肌梗死行经皮冠状动脉介入治疗(PCI)血清炎症因子的改变及其与预后的关系。方法:选择126例拟行PCI治疗的急性心肌梗死患者为研究对象,比较PCI手术前后血清超敏C反应蛋白(hs-CRP)及肿瘤坏死因子α(TNF-α)的改变。同时比较PCI术后3月发生心血管事件患者与未发生心血管事件患者术后12h血清hs-CRP及TNF-α的差别。结果:患者PCI术后血清hs-CRP及TNF-α水平均显著升高,与术前相比差别具有统计学意义(P<0.05);PCI术后3月发生心血管事件患者PCI术后12h血清hs-CRP及TNF-α水平显著高于未发生心血管事件患者(P<0.05);Logistic回归结果显示:hs-CRP及TNF-α与心血管事件发生率显著相关。结论:急性心肌梗死行PCI患者术后发生急性炎症反应,hs-CRP及TNF-α水平升高与患者心血管事件发生密切相关,可作为评估预后的血清学指标。     

SPECT心肌灌注显像对急性心肌梗死患者PCI术后疗效评估

目的:探讨用单光子发射型计算机断层(single photon emission computedtomography,SPECT)心肌灌注显像,评估心肌梗死(AMI)经冠脉介入治疗(PCI)后的心肌灌注疗效。方法:采用99mTc-tetrofosmin(P53)SPECT心肌灌注显像对54例行PCI治疗的AMI患者评估心肌灌注情况,并追踪记录6个月内心脏事件发生率。结果:SPECT显示无复流组22例,有复流组32例,两组心肌梗死患者近期预后差异有统计学意义(P<0.05)。无复流组不良事件发生率较有复流组有增加趋势;另外,急诊PCI组的预后明显好于择期PCI组,差异有统计学意义(P<0.05)。结论:SPECT心肌灌注显像可对AMI患者梗死相关血管(IRA)再通治疗疗效进行可靠的无创性评价。     

胸阻抗法心排血量比较直接PCI和延迟PCI对急性ST段抬高型心肌梗死患者心功能的影响

目的:采用胸阻抗法心排血量检测和比较直接和延迟经皮冠状动脉介入术(PCI)对急性ST段抬高型心肌梗死(STEMI)患者心功能的影响。方法:收集2016年1月-2018年6月于解放军南部战区海军第一医院收治的114例STEMI患者完整资料,分为直接PCI组48例,延迟PCI组40例,对照组(未行任何再灌注治疗)26例。采用胸阻抗法心排血量检测各组患者治疗后3天、6个月的每搏输出量(SV)、心指数(CI)、左心收缩力指数(CTI)、射血分数(EF)等心功能参数,并随访患者6个月内因心力衰竭再住院的情况。结果:治疗后6个月,直接PCI组和延迟PCI组SV、CI、CTI、EF均显著高于对照组,且直接PCI组SV、CTI、EF明显高于延迟PCI组,各组间差异具有统计学意义(P<0.05)。直接PCI组和延迟PCI组6个月内因心力衰竭再住院分别为2.08%和5%,均显著低于对照组(19.23%),差异具有统计学意义(P<0.05)。结论:直接和延迟PCI均能改善STEMI患者中远期心功能,且直接PCI效果更为显著。     

术前负荷剂量阿托伐他汀对STEMI急诊PCI患者的Hs-CRP、BNP水平及心功能影响

目的:研究手术前负荷剂量阿托伐他汀对ST段抬高型心肌梗死(STEMI)急诊经皮冠状动脉介入(PCI)患者的高敏C反应蛋白(Hs-CRP)、血浆脑钠肽(BNP)水平及心功能的影响。方法:选取我院2014年9月到2016年4月间收治的ST段抬高型心肌梗死(STEMI)患者96例,均行急诊经冠状动脉介入术(PCI),采用随机数字法将其分为对照组和观察组,每组各48例。观察组患者术前口服阿托伐他汀80 mg,术后口服阿托伐他汀40 mg/d;对照组患者仅术后口服阿托伐他汀40 mg/d。比较两组患者术后灌注情况、血清高敏C反应蛋白(hs-CRP)、B型脑钠肽(BNP)、基质金属蛋白酶9(MMP-9)、肌酸磷化脢-同功脢(CK-MB)和肌钙蛋白(c Tn I)水平的变化。结果:治疗后,观察组的ST段回落率、TIMI血流分级(CTFC)、TIMI3级和TMP3级比例均明显高于对照组(P0.01),血清hs-CRP、BNP及MMP-9水平、血清CK-MB和c Tn I峰值及持续时间均明显低于对照组(P0.01)。结论:PCI术前给予80mg阿托伐他汀对STEMI患者的疗效显著,可提高心肌血流灌注恢复质量,抑制炎症反应,改善心室收缩功能,且安全性高。     

冠状动脉介入治疗对冠心病患者Caspase-3,9水平的影响

目的：通过对冠心病患者经皮冠状动脉介入治疗（PCI）前后血清Caspase-3,9水平变化的观察,探讨冠状动脉介入治疗对冠心病患者血清Caspase-3,9水平的影响。方法：冠状动脉介入组（PCI组）30例和单纯造影组（CAG组）29例,在术前0.5h,术后3h,术后6h,术后12h,术后24h,术后48h分别测定血清Caspase-3,9水平。结果：CAG组术前与术后的血清Caspase-3,9水平差异均无统计学意义,PCI组术后3h、6h的Caspase-3水平较术前0.5h均有降低趋势,差异均有统计学意义（P〈0.05）,PCI组术后48h的Caspase-9水平与术后3h、6h相比均有升高趋势,差异均有统计学意义（P〈0.05）。结论：PCI术后狭窄或闭塞的冠状动脉血管重新恢复血供,血清中Caspase-3,9水平在PCI术后先降低后又逐渐升高,提示再灌注后可出现细胞的凋亡程度加重,血清中Caspase-3,9的水平可作为心肌再灌注损伤后细胞凋亡程度的评估指标并可作为诊断临床症状不典型的再灌注损伤的一个指标。PCI术可有效改善心肌血供,减少因术前缺血缺氧造成的细胞凋亡,但PCI术后再灌注损伤可进一步加重细胞凋亡。     

血栓抽吸联合PCI术前阿托伐他汀强化治疗急性ST段抬高型心肌梗死

目的:探讨急性ST段抬高型心肌梗死急诊经皮冠状动脉介入治疗(PCI)中应用GOODMAN血栓抽吸装置联合术前阿托伐他汀强化治疗对心肌组织灌注及临床预后的影响.方法:选择梗死相关血管心肌梗死溶栓试验血流0级的急性ST段抬高型心肌梗死患者80例,随机分为血栓抽吸联PCI术前阿托伐他汀强化治疗组(试验组)40例和标准PCI治疗组(对照组)40例.比较两组患者术后心肌梗死溶栓试验(TIMI)血流分级、TIMI心肌灌注分级(TMPG)、心电图ST段回落百分比、左心室射血分数(LVEF)及住院期间主要心血管不良事件(MACE).结果:试验组TIMI血流分级、TMPG、ST段回落百分比、LVEF均明显优于对照组(P＜0.05).两组患者住院期间MACE发生率比较,差异无统计学意义(P＞0.05).结论:在急性ST段抬高型心肌梗死急诊经皮冠状动脉介入治疗(PCI)中应用血栓抽吸联合术前阿托伐他汀强化治疗安全可行,可有效清除冠状动脉内血栓,改善心肌组织灌注及术后心脏功能,并且不增加主要心血管事件的发生率.     

The Comparison of the Outcomes between Primary PCI,Fibrinolysis, and No Reperfusion in Patients ≥ 75 Years Old with ST-Segment Elevation Myocardial Infarction: Results from the Chinese Acute Myocardial Infarction (CAMI) Registry

BackgroundOnly a few randomized trials have analyzed the clinical outcomes of elderly ST-segment elevation myocardial infarction (STEMI) patients (≥ 75 years old). Therefore, the best reperfusion strategy has not been well established. An observational study focused on clinical outcomes was performed in this population.MethodsBased on the national registry on STEMI patients, the in-hospital outcomes of elderly patients with different reperfusion strategies were compared. The primary endpoint was defined as death. Secondary endpoints included recurrent myocardial infarction, ischemia driven revascularization, myocardial infarction related complications, and major bleeding. Multivariable regression analysis was performed to adjust for the baseline disparities between the groups.ResultsPatients who had primary percutaneous coronary intervention (PCI) or fibrinolysis were relatively younger. They came to hospital earlier, and had lower risk of death compared with patients who had no reperfusion. The guideline recommended medications were more frequently used in patients with primary PCI during the hospitalization and at discharge. The rates of death were 7.7%, 15.0%, and 19.9% respectively, with primary PCI, fibrinolysis, and no reperfusion (P < 0.001). Patients having primary PCI also had lower rates of heart failure, mechanical complications, and cardiac arrest compared with fibrinolysis and no reperfusion (P < 0.05). The rates of hemorrhage stroke (0.3%, 0.6%, and 0.1%) and other major bleeding (3.0%, 5.0%, and 3.1%) were similar in the primary PCI, fibrinolysis, and no reperfusion group (P > 0.05). In the multivariable regression analysis, primary PCI outweighs no reperfusion in predicting the in-hospital death in patients ≥ 75 years old. However, fibrinolysis does not.ConclusionsEarly reperfusion, especially primary PCI was safe and effective with absolute reduction of mortality compared with no reperfusion. However, certain randomized trials were encouraged to support the conclusion.     

Atrial fibrillation after but not before primary angioplasty for ST-segment elevation myocardial infarction of prognostic importance

Aim

In patients with ST-segment elevation myocardial infarction (STEMI), it is uncertain whether atrial fibrillation has prognostic implications. There may be a difference between atrial fibrillation before and after reperfusion therapy.

Methods and results

In patients with STEMI treated with primary percutaneous coronary intervention (PCI), ECGs were analysed before and after primary PCI. Of the 1623 patients with electrocardiographic data before primary PCI, 53 patients (3.3%) had atrial fibrillation. Patients with atrial fibrillation were older, were more often female, and less often had anterior MI location. Of the 1728 patients with electrocardiographic data after primary PCI, 52 patients (3.0%) had atrial fibrillation. Atrial fibrillation was more common in older patients and in those with Killip class >1. Also patients with occlusion of the right coronary artery or TIMI flow 0 before primary PCI more commonly had AF after the procedure. Not successful reperfusion was also associated with a higher incidence of AF after primary PCI. Although both atrial fibrillation before and after primary PCI were associated with increased mortality, multivariable analyses, adjusting for differences in age, gender and Killip class on admission, revealed that atrial fibrillation after PCI (OR 3.69, 95% CI 1.87–7.29) but not before PCI (OR 1.86, 95% CI 0.89–3.90) was independent and statistically significantly associated with long-term mortality.

Conclusion

In patients with STEMI, atrial fibrillation after but not before primary PCI has independent prognostic implications. Possibly, atrial fibrillation after the PCI is a symptom of failed reperfusion and a sign of heart failure.     

Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes

Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI.     

冠脉内注射替罗非班不同给药方式对急性心肌梗死介入治疗术中血流异常的影响

目的：比较急性心肌梗死介入治疗中冠脉内常规给予以及必要时给予血小板膜糖蛋白（GP）Ⅱb／Ⅲa受体拮抗剂替罗非班两种给药方式对冠脉血流异常的影响,寻找较好的替罗非班用药方式。方法：入选九四医院2005年1月至2008年10月急性心肌梗死直接PCI患者58例,随机分成常规给药组（血管开通前所有患者冠状动脉内均注射替罗非班,n=30）与必要时给药组（血管开通后即时造影显示TIMI血流≤2级者冠脉内注射替罗非班,TIMI血流3级者不给药,n=28）,观察支架植入后30分钟TIMI血流、30天内主要不良心血管事件（MACE）、出血以及血小板减少情况。结果：必要给药组冠脉内给药可显著改善冠脉血流（TIMI3级给药前46．4％,给药后75％,P〈0．05）,常规给药组支架植入后30分钟TIMI3级获得率高于必要给药组（96．7％比75％,P〈0．05）,MACE、出血和血小板减少事件两组之间差异无统计学意义。结论：冠脉内给予替罗非班可有效降低急性心肌梗死PCI术中血流异常情况,血管开通前冠脉内常规给药方式优于必要时给药方式。     

Nicorandil in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute myocardial infarction (AMI).

Methods and Results

We performed a systematic review of randomized controlled trials (RCTs) comparing treatment with nicorandil prior to reperfusion therapy with control (placebo or no nicorandil) in patients who suffered from AMI and performed primary PCI. PubMed, EMBASE and CENTRAL databases and other sources were searched without language and publication restriction. 14 trials involving 1680 patients were included into this meta-analysis. Nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) flow grade ≤2 (risk ratio [RR], 0.57; 95% confidence interval [CI]: 0.42 to 0.79), the Timi frame count (TFC) (mean difference [MD], -5.19; 95% CI: -7.13 to -3.26), increased left ventricular ejection fraction (LVEF) (%) (MD, 3.08; 95% CI: 0.79 to 5.36), and reduced the incidence of ventricular arrhythmia (RR, 0.53; 95% CI: 0.37 to 0.76) and congestive heart failure (CHF) (RR, 0.41; 95% CI: 0.22 to 0.75). No difference in the pear creatine kinase (CK) value (MD, -290.19; 95% CI: -793.75 to 213.36) or cardiac death (RR, 0.39; 95% CI: 0.09 to 1.67) was observed.

Conclusions

Nicorandil prior to reperfusion is associated with improvement of coronary reflow as well as suppression of ventricular arrhythmia, and further improves left ventricular function in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies.     

Oxidative stress and inflammatory response during and following coronary interventions for acute myocardial infarction

BACKGROUND: In acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), myocardial injury results from complex processes during both ischemia and reperfusion. Release of reactive oxygen species (ROS) may contribute to the accumulated myocardial damage. AIMS: To examine by frequent sampling of peripheral blood oxidative stress and early inflammation in patients undergoing primary PCI for AMI. Secondly, to assess whether a correlation exists between these parameters and the extent of myocardial damage. METHODS: Sixteen patients undergoing primary PCI within 6 h of AMI onset were included. Peripheral blood was sampled at start of procedure (t0) and repeatedly over 24 h following reperfusion. Main plasma analyses were: 8-iso-PGF2alpha (oxidative stress), 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); and troponin-T (myocardial injury). Additional analyses included: total antioxidant status (TAS); vitamins; hsCRP and lipids. RESULTS: 8-Iso-PGF2alpha increased following restoration of blood flow, returned to t0 values after 3 h and was reduced below t0 the following day. TAS decreased significantly from t0 to the next day. There was no significant correlation between 8-iso-PGF2alpha and troponin T values. 15-Keto-dihydro-PGF2alpha was elevated during the first hour. There was a major rise in hsCRP after 24 h. CONCLUSION: Following reperfusion by primary PCI in AMI, oxidative stress and an inflammatory response are induced immediately. A rise in 8-iso-PGF2a during ischemia indicate that ROS generation may also take place during severely reduced coronary blood flow and hypoxia. No direct relationship between 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha and troponin T was evident. The present study adds to the increasingly complex pathophysiological roles of ROS acting both as signal molecules and as mediators of tissue injury.     

Dynamic changes and clinical significance of serum tryptase levels in STEMI patients treated with primary PCI

Abstract

Objective: To investigate the dynamic changes in serum tryptase levels and their association with clinical data in patients with acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods: Serum tryptase levels were measured in 99 STEMI patients and 25 control subjects.

Results: Tryptase levels were significantly increased at admission, and descended after primary PCI. Tryptase levels at 0.5, 2 and 6?h after PCI were negatively correlated with the percentage of ST-segment resolution (STR) as well as left ventricular ejection fraction (LVEF).

Conclusions: High tryptase levels after PCI were associated with poor myocardial reperfusion and poor cardiac function.