Early heparin preconditioning on infarction related vascular blood flow and inflammatory factors and long term cardiac function in STEMI patients undergoing emergency interventional therapy
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摘要: 目的 探讨肝素早期预处理对急诊介入治疗急性ST段抬高型心肌梗死(ST segment elevation myocardial infarction，STEMI)患者的梗死相关血管(infarct related artery, IRA)血流及对炎性因子、远期心功能的影响。方法 选取济宁市第一人民医院急诊科2020年1月—2022年2月收治的STEMI患者58例，男38例，女20例；年龄41~72岁，平均(55.6±13.8)岁。所选择患者按照Doll’s临床病例随机分成两组：常规治疗组，即A组(29例)；早期肝素预处理组，即B组(29例)。两组患者均为单绕途径，即绕行CCU，直接通过急诊至导管室，并实施了急诊直接经皮冠状动脉介入术(primary percutaneous coronary intervention，PPCI)，A组为急诊科嚼服双抗血小板药物，完善心肌坏死标记物及炎性因子检测：肌钙蛋白Ⅰ(cTnⅠ)、肌红蛋白(myoglobin, Myo)、肌酸激酶同工酶(creatine kinase isoenzyme, CK-MB)等及超敏C反应蛋白(C-reactive protein，CRP)后至导管室直接实施急诊PCI，术后继续常规治疗。B组在A组基础上，急诊科用普通肝素预处理(剂量100 U/kg+生理盐水5 mL静脉推注)后直达导管室。两组患者均观察治疗前后IRA造影剂显示情况，即冠脉远端血流(thrombolysis in myocardial infarction, TIMI)分级和评价再灌注情况；术后即测定心电图与急诊科心电图对比，观察ST段回落情况。术后2 h测定cTnI、CK-MB、Mb、CRP。两组出院1个月、3个月、6个月的心脏超声测定左室射血分数(left ventricular ejection fraction，LVEF)、左室收缩末期容积(left ventricular end systolic volume，LVESV)、左室舒张末期容积(left ventricular end diastolic volume, LVEDV)指标。记录住院期间及术后半年内出血事件及主要不良心血管事件(major adverse cardiovascular events，MACE)。结果 与A组比较，B组治疗前IRA再通比例高，两组差异有统计学意义(P < 0.05)；与A组比较，B组术后慢血流、无复流比例减少，TIMI 3级慢、快血流比例增加，差异有统计学意义(P < 0.05)。与A组比较，B组术后CK-MB、cTnI、Myo、CRP水平较入院前明显下降，两组差异有统计学意义(均P < 0.05)。ST段回落比例均下降，两组对比差异无统计学意义(P>0.05)。A组与B组术后1个月、3个月超声指标比较差异无统计学意义(P>0.05)；术后6个月B组较A组LVESV、LVEDV减少，LVEF增加，差异有统计学意义(P < 0.05)。两组MACE比较，住院期间A组仅再灌注心律失常发生较B组高，差异有统计学意义(P < 0.05)。住院期间及出院后半年内，两组出血率比较差异无统计学意义(P>0.05)。出院至半年内MACE发生率比较，A组发生心衰比例高于B组，差异有统计学意义(P < 0.05)。结论 STEMI患者直接PPCI治疗前早期肝素预处理可以减轻心肌进一步损伤和炎症反应，大大提高了心肌存活率，从而改善了患者远期心功能，这与肝素预处理能明显改善罪犯血管早期再灌注，减轻血栓负荷有关，从而改善了患者远期心功能，且出血风险并未增加，值得临床大力推广应用。
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关键词:
- 预处理 /
- 急性ST段抬高型心肌梗死 /
- 经皮冠状动脉介入术 /
- 梗死相关动脉
Abstract: Objective To investigate the effects of early heparin pretreatment on infarct related artery(IRA) blood flow, inflammatory factors, and long-term cardiac function in patients with acute ST segment elevation myocardial infarction(STEMI) undergoing emergency intervention treatment.Methods Fifty-eight STEMI patients, including 38 males and 20 females, aged 41-72, with mean(55.6±13.8) years, admitted to the emergency department of our hospital from January 2020 to February 2022, were selected. The selected patients were randomly divided into a conventional group based on Doll's clinical cases, namely Group A(29 cases) and an early heparin pretreatment group, namely Group B(29 cases). The two selected groups of patients underwent a single bypass pathway, which involves bypassing the CCU and directly entering the catheterization room through the emergency department and emergency direct percutaneous coronary intervention(PPCI) was performed. Group A received dual antiplatelet drugs and improved detection of myocardial necrosis markers and inflammatory factors, including troponin Ⅰ (cTnⅠ), myoglobin (Myo), creatine kinase isoenzyme (CK-MB), and high sensitivity C-reactive protein (CRP), etc. Emergency PCI was directly performed in the catheter room, and routine treatment continued after the surgery. On the basis of Group A, Group B was pretreated with ordinary heparin(dosage of 100 U/kg+5 mL of physiological saline intravenously) in the emergency department and then directed to the catheter room. Both groups of patients were observed for the display of IRA contrast agent before and after treatment, including the classification of distal coronary artery flow(TIMI) and evaluation of reperfusion status. After the surgery, the electrocardiogram was measured and compared with the electrocardiogram of the emergency department to observe the ST segment regression. CTnI, CK-MB, Mb, CRP were measured 2 hours after surgery. Left ventricular ejection fraction(LVEF), left ventricular end systolic volume(LVESV), and left ventricular end diastolic volume(LVEDV) were measured by echocardiography at 1 month, 3 months, and 6 months after discharge in two groups. Record bleeding events and major adverse cardiovascular events(MACE) within six months after surgery during hospitalization.Results Compared with Group A, Group B had a higher proportion of IRA recanalization before treatment, with a statistically significant difference(P < 0.05). The proportion of slow blood flow and no reflow decreased after surgery, while the proportion of TIMI grade 3 slow and fast blood flow increased, with a statistically significant difference(P < 0.05). Compared with Group A, the postoperative levels of CK-MB, cTnI, Myo, and CRP in Group B decreased significantly compared to before admission, with statistically significant differences(P < 0.05). The proportion of ST segment regression decreased, and there was no statistically significant difference between the two groups(P>0.05). There was no statistically significant difference in ultrasound indicators between Group A and Group B at 1 and 3 months after surgery(P>0.05). At 6 months after surgery, LVESV and LVEDV in Group B decreased compared to Group A, while LVEF increased, with a statistically significant difference(P < 0.05). When comparing MACE, during hospitalization, only group A had a higher incidence of reperfusion arrhythmia compared to group B, with a statistically significant difference(P < 0.05). There was no statistically significant difference in bleeding rates between the two groups during hospitalization and within six months after discharge(P>0.05). The incidence of MACE within six months after discharge was compared, and the proportion of heart failure in Group A was higher than that in Group B, with a statistically significant difference(P < 0.05).Conclusion Early heparin pretreatment before PPCI treatment in STEMI patients can alleviate further myocardial injury and inflammatory response, greatly improve myocardial survival rate, and thus improve long-term cardiac function. This is related to the significant improvement of early reperfusion of culprit blood vessels and the reduction of thrombus burden by heparin pretreatment, thereby improving long-term cardiac function of patients, and the risk of bleeding is not increased. It is worthy of clinical promotion and application. -
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表 1 两组术后TIMI分级出现NRP及SRP情况比较
例(%) TIMI A组(29例) B组(29例) P NRP 17(39.5) 11(25.6) 0.017 SRP 6(14.0) 2(4.7) 0.031 
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表 2 两组IRA初始血流比较
例(%) 项目 A组(29例) B组(29例) P TIMI分级 0级 27(93.1) 10(34.5) < 0.001 1级 2(6.9) 13(44.8) < 0.001 >1级 0 6(20.7) 0.016 ST段回落 26(89.7) 24(82.8) 0.087
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表 3 两组心肌损伤标记物、炎性因子比较
X±S 项目 A组(29例) B组(29例) 术前 术后 术前 术后 CK-MB/(ng/mL) 27.8±2.1 16.7±1.81) 28.3±2.0 10.2±1.51) cTnI/(ng/mL) 6.8±0.8 4.4±0.61) 7.0±0.6 2.3±0.51) Myo/(ng/mL) 215.6±15.6 147.6±15.61) 210.8±14.7 110.2±10.41) BNP/(pg/mL) 860.6±47.8 560.1±41.11) 857.2±57.3 307.3±48.51) CRP/(mg/L) 34.3±5.1 24.6±3.71) 33.9±4.8 15.7±3.11) 与同组术前比较，1)P < 0.05。
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表 4 两组不同时间段超声指标比较
X±S 项目 A组 B组 LVEF/% 出院1个月 40.2±4.5 43.8±4.3 出院3个月 45.3±4.2 47.2±3.7 出院6个月 51.6±2.4 61.6±2.31) LVESV/mL 出院1个月 68.1±6.7 69.2±5.3 出院3个月 64.4±3.9 62.2±3.1 出院6个月 62.0±3.1 53.1±2.71) LVEDV/mL 出院1个月 51.3±4.1 50.6±4.7 出院3个月 47.4±2.5 40.6±1.4 出院6个月 43.4±2.0 36.5±2.11) 与A组比较，1)P < 0.05。
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表 5 两组住院期间及半年内出血、MACE比较
例(%) 项目 A组
(29例)B组
(29例)P 住院期间 术后2 h内再灌注心律失常 11(37.9) 2(6.9)1) 0.002 术后24 h内心绞痛 5(19.1) 6(22.8) 0.471 心功能恶化 3(10.3) 2(6.9) 0.365 恶性心律失常 4(13.8) 0 0.04 致死性出血 0 0 1.000 非致死性出血 4(13.8) 3(10.3) 0.454 急性支架内血栓 0 0 0.301 靶血管再次血运重建 0 0 1.000 术后半年内 心绞痛发作 6(20.7) 5(17.2) 0.528 恶性心律失常 1(3.4) 0 0.410 出血事件 4(13.8) 3(10.3) 0.467 心衰(心功能>3级) 5(17.2) 1(3.4)1) 0.021 慢性支架内血栓 0 0 1.00 再次住院 4(13.8) 1(3.4)1) 0.031 与A组比较，1)P < 0.05。
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