预防性冠状动脉内应用山莨菪碱对急性下壁心肌梗死行直接经皮冠状动脉介入治疗患者心肌再灌注的保护效应

Protective Effect of Intracoronary Injection of Anisodamine Before Myocardial Reperfusion in Acute Inferior Myocardial Infarction Patients Undergoing Primary PCI

目的:探讨预防性冠状动脉(冠脉)内应用山莨菪碱对接受直接经皮冠状动脉介入治疗(PCI)的急性下壁心肌梗死(AIMI)患者的心肌再灌注的保护效应及其机制。方法:本研究为单中心前瞻随机对照研究,入选2014-01至2016-03发病12 h内接受直接PCI的AIMI患者。符合条件的患者随机分为山莨菪碱组[n=72,梗死相关动脉(IRA)开通前冠脉内给予山莨菪碱1 500μg/3 ml]和对照组(n=71,IRA开通前冠脉内给予等量生理盐水3 ml)。对所有量化的冠脉血流及心肌组织灌注指标进行判定,包括初始及术后心肌梗死溶栓治疗临床试验(TIMI)血流分级、TIMI心肌灌注分级(TMPG)。以肌酸激酶同工酶(CK-MB)及心肌肌钙蛋白I(c Tn I)峰值水平评估心肌梗死面积。术前及术后24 h各查一次炎症反应标志物高敏C反应蛋白(hsCRP)、白细胞介素(IL)-6、P-选择素和细胞间黏附分子(ICAM)-1。入院时及术后90 min各查心电图一次,以ST段回落(STR)程度作为反映心肌再灌注水平的指标,并把两组完全STR的比例定义为本研究的主要终点。随访术后30天及6个月的主要不良心血管事件(MACE)。应用多变量Logistic回归分析探讨完全STR的相关因素。结果:PCI后,山莨菪碱组TIMI血流3级及TMPG 3级的患者比例均显著高于对照组(TIMI血流3级:91.7%vs 77.5%,P=0.03;TMPG 3级:80.6%vs 60.6%,P=0.01)。山莨菪碱组患者的心电图ST段明显回落,ST段抬高振幅总和(ΣSTE)从(10.0±4.2) mm下降至(5.8±1.7) mm,两组完全STR的比例差异有统计学意义(69.4%vs 50.7%,P=0.03)。再灌注后,山莨菪碱组有4例(5.6%)患者发生再灌注性过缓心律失常;而对照组有42例(59.2%)患者发生再灌注性过缓心律失常。多变量Logistic回归分析显示:冠脉舒张压降低(OR=1.298,95%CI:1.155~1.457,P<0.01)及心率减慢(OR=1.251,95%CI:1.087~1.440,P=0.002)是不完全STR的独立危险因素,冠脉内应用山莨菪碱为完全STR的保护性因素(OR=0.059,95%CI:0.014~0.255,P<0.01)。PCI后24 h时,两组炎症反应标志物水平均升高,但山莨菪碱组炎症反应标志物水平显著低于对照组(P<0.01)。随访30天时,对照组有1例患者新发心肌梗死,1例患者需要靶血管血运重建。随访6个月时,山莨菪碱组和对照组分别有1例和5例患者出现MACE(P=0.21)。结论:预防性冠脉内应用山莨菪碱可减少AIMI-PCI无复流的发生,改善心肌灌注,用药安全可行。

Objectives： To investigate whether intracoronary administration of anisodamine before myocardial reperfusion could reduce/avoid no-reflow phenomenon and improve myocardial reperfusion in acute inferior myocardial infarction（AIMI） patients undergoing primary percutaneous coronary intervention（PCI）.Methods： In this single-center prospective randomized controlled study, we enrolled patients suffering from AIMI within 12 hours undergoing primary PCI from January 2014 to March 2016. Eligible patients were randomly divided into two groups：Anisodamine group, 72 cases, intracoronary administration of anisodamine 1500 μg/3 ml before myocardial reperfusion;Control group, 71 cases, intracoronary administration of saline 3 ml before myocardial reperfusion. All patients received transradial coronary intervention. Quantitative coronary angiography tissue perfusion indexes [including the initial thrombolysis in myocardial infarction（TIMI）, postoperative TIMI, and TIMI myocardial perfusion grade（TMPG）] were judged by two interventional cardiologists. Myocardial infarct size was estimated by peak levels of CK-MB and c Tn I. Inflammatory markers including hs-CRP, IL-6, P-selectin and ICAM-1 were tested before and 24 h after PCI. Electrocardiography was recorded on admission and at 90 min after PCI. A decrease in the sum of ST-segment elevation by ≥ 70% was categorized as complete ST-segment resolution（STR） and used as an index of myocardial reperfusion and the primary end point of this study. Major adverse cardiovascular events were evaluated within 30 days and 6 months after discharge. Multivariate logistic regression analysis was used to explore the related factors associated with complete STR.Results：After PCI, the proportions of TIMI 3（91.7% vs 77.5%, P =0.03） and TMPG 3（80.6% vs 60.6%, P =0.01） were significantly higher in anisodamine group than in control group. ST segments were significantly resolved, ΣSTE reduced from（10.0±4.2） mm to（5.8±1.7） mm in anisodamine group. The percentage of complete STR was statistically higher in anisodamine group than in control group（69.4% vs 50.7%, P=0.03）. After PCI, there were 4 cases of bradycardia in anisodamine group and 42 cases bradycardia in control group. Multivariate Logistic regression analysis showed that low coronary diastolic pressure（OR=1.298, 95% CI： 1.155-1.457, P〈0.01） and slow heart rate（OR=1.251, 95% CI： 1.087-1.440, P=0.002） were independent risk factors of incomplete STR, while anisodamine administration was a protective factor for complete STR（OR=0.059, 95% CI： 0.014-0.255, P〈0.01）. At 24 h after PCI, the levels of inflammatory markers increased in both two groups, but were significantly lower in anisodamine group compared to control group（P〈0.01）. Within 30-day after PCI, there was one patient developing new MI and another patient needing target vessel revascularization in control group. At the end of 6-month follow up, one MACE and 5 MACEs occurred in anisodamine group and control group respectively（P=0.21）.Conclusions：Intracoronary administration of anisodamine before reperfusion is safe and can reduce no-reflow and improve myocardial perfusion in AIMI patients undergoing PCI.