袁馳，柯永勝，柯可

· 論著 ·

急性ST段抬高型心肌梗死患者行急診PCI無(wú)復(fù)流的危險(xiǎn)因素分析

袁馳1，柯永勝1，柯可2

目的 分析急性ST段抬高型心肌梗死（STEMI）患者行急診經(jīng)皮冠狀動(dòng)脈介入治療（PCI）后出現(xiàn)無(wú)復(fù)流的相關(guān)危險(xiǎn)因素。方法 選擇2012年5月～12月于皖南醫(yī)學(xué)院第一附屬弋磯山醫(yī)院心內(nèi)科就診STEMI且行急診PCI的患者166例，其中男性139例，女性27例，年齡36～91（63.10±11.96）歲。按照血管機(jī)械開(kāi)通后的造影情況分為正常灌注組（142例）和無(wú)復(fù)流組（24例）。采集患者缺血時(shí)間、合并基礎(chǔ)疾病等一般臨床資料，入院即刻和入院后采靜脈血，檢測(cè)中性粒細(xì)胞百分比、血小板計(jì)數(shù)（PLT）、低密度脂蛋白膽固醇（LDL-C）水平等，測(cè)定病變血管直徑和靶病變長(zhǎng)度。結(jié)果 無(wú)復(fù)流組缺血時(shí)間和中性粒細(xì)胞百分比均高于正常灌注組，差異有統(tǒng)計(jì)學(xué)意義（P均＜0.01）。結(jié)果顯示，缺血時(shí)間＞6 h（OR=1.578，95%CI：1.245～2.000）和中性粒細(xì)胞百分比＞80.0%（OR=3.405，95%CI：1.027～11.293）均為急診PCI術(shù)后無(wú)復(fù)流的危險(xiǎn)因素。結(jié)論 急性ST段抬高型心肌梗死行急診PCI的患者，缺血時(shí)間明顯延長(zhǎng)，中性粒細(xì)胞百分比明顯升高，發(fā)生無(wú)復(fù)流的概率會(huì)更高。

急性ST段抬高型心肌梗死；急診PCI；無(wú)復(fù)流

急性ST段抬高型心肌梗死（STEMI）是最常見(jiàn)的致死原因之一[1]。對(duì)于STEMI患者，盡管行急診經(jīng)皮冠狀動(dòng)脈介入治療（PCI）是最理想的治療策略，但無(wú)復(fù)流發(fā)生率為15%～60%[2]。無(wú)復(fù)流定義為行PCI后，盡管梗死相關(guān)血管開(kāi)通，但心肌組織無(wú)血流灌注[3]。無(wú)復(fù)流可導(dǎo)致心肌梗死面積擴(kuò)大、腦卒中、負(fù)性左室重構(gòu)、心力衰竭及死亡率增高等一系列惡性臨床事件，降低PCI帶來(lái)的獲益[4-6]。目前無(wú)復(fù)流的機(jī)制尚未完全闡明，多數(shù)學(xué)者認(rèn)為由微血管栓塞、遠(yuǎn)端栓塞、微血管痙攣等導(dǎo)致[3]。同時(shí)涉及多種因素，包括內(nèi)皮損傷、微血管損傷、血小板和中性粒細(xì)胞以及內(nèi)皮細(xì)胞的互相作用[7]。本研究主要回顧分析了STEMI行急診PCI出現(xiàn)無(wú)復(fù)流的危險(xiǎn)因素，為臨床防治提供依據(jù)。

1 資料與方法

1.1 研究對(duì)象和分組 選擇2012年5月～12月于皖南醫(yī)學(xué)院第一附屬弋磯山醫(yī)院心內(nèi)科就診STEMI且行PCI的患者166例，其中男性139例，女性27例，年齡36～91歲，平均63.10±11.96。所有患者均在發(fā)病12 h內(nèi)入院，確診為STEMI，診斷標(biāo)準(zhǔn)參考第3版《心肌梗死通用定義》[8]。無(wú)復(fù)流定義為盡管罪犯血管開(kāi)通，但造影時(shí)TIMI血流≤2級(jí)[9]。排除標(biāo)準(zhǔn)：①NSTEMI患者；②由于血管鈣化等原因，未能成功置入支架的患者；③存在血液系統(tǒng)疾病的患者；④既往行PCI患者；⑤合并嚴(yán)重的感染、甲亢、癌癥、自身免疫病等；⑥數(shù)據(jù)不完整，影響統(tǒng)計(jì)分析的患者。按照血管機(jī)械開(kāi)通后的造影情況分為正常灌注組（n=142）和無(wú)復(fù)流組（n=24）。

1.2 主要觀察指標(biāo) 采集患者入院后病史資料，如缺血時(shí)間、合并基礎(chǔ)疾病等。所有患者均于急診PCI前抽取靜脈血，采用SYSMEX-XT1800i全自動(dòng)血細(xì)胞分析儀，檢測(cè)中性粒細(xì)胞百分比、血小板計(jì)數(shù)（PLT）、血小板平均容積（MPV）。入院后擇期采靜脈血，采用HITACHI 7600全自動(dòng)生化分析儀（試劑由HITACHI公司提供）檢測(cè)低密度脂蛋白膽固醇（LDL-C）水平，行PCI時(shí)觀測(cè)病變血管直徑和靶病變長(zhǎng)度。

1.3 急診PCI 術(shù)前常規(guī)嚼服阿司匹林300 mg和氯吡格雷300 mg，結(jié)合心電圖表現(xiàn)判斷病變血管，若病變血管可見(jiàn)血栓影，使用抽吸導(dǎo)管抽吸血栓，并經(jīng)導(dǎo)管推注GP IIb/IIIa 受體拮抗劑（替羅非班）。術(shù)后皮下注射低分子肝素5～7 d，口服阿司匹林100 mg/d，氯吡格雷75 mg/d，口服血管緊張素轉(zhuǎn)化酶抑制劑、β受體阻滯劑（若無(wú)低血壓、顯著心動(dòng)過(guò)緩等禁忌）和他汀類(lèi)藥物。

1.4 統(tǒng)計(jì)學(xué)處理 所有的數(shù)據(jù)均采用SPSS 19.0統(tǒng)計(jì)軟件進(jìn)行分析。計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差（±s）表示，兩組間均數(shù)的比較采用t檢驗(yàn)，計(jì)數(shù)資料采用例數(shù)（構(gòu)成比）表示，組間比較采用χ2檢驗(yàn)。采用Logistic回歸分析急診PCI后無(wú)復(fù)流的影響因素。P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 兩組臨床資料比較 無(wú)復(fù)流組與正常灌注組在冠狀動(dòng)脈病變支數(shù)、病變血管直徑、靶病變長(zhǎng)度、PLT、MPV、LDL-C等方面比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（P均＞0.05）。在無(wú)復(fù)流組中，未觀察到罪犯血管為回旋支、左主干。無(wú)復(fù)流組缺血時(shí)間和中性粒細(xì)胞百分比均高于正常灌注組，差異有統(tǒng)計(jì)學(xué)意義（P均＜0.01）（表1）。

2.2 多因素Logistic回歸分析 為進(jìn)一步排除混雜因素的影響，以急診PCI后是否出現(xiàn)無(wú)復(fù)流作為因變量，引入單因素分析有顯著差異的因素進(jìn)行Logistic回歸分析。結(jié)果顯示：缺血時(shí)間＞6 h（OR=1.578，95%CI：1.245～2.000）和中性粒細(xì)胞百分比＞80.0%（OR=3.405，95%CI：1.027～11.293）均為急診PCI術(shù)后無(wú)復(fù)流的危險(xiǎn)因素（表2）。

表1 兩組患者臨床資料比較

表2 無(wú)復(fù)流發(fā)生的多因素回歸分析

3 討論

無(wú)復(fù)流與心肌梗死面積大小、近期以及遠(yuǎn)期的死亡率有關(guān)，預(yù)測(cè)預(yù)后[10]。本研究的無(wú)復(fù)流發(fā)生率為14.5%，與之前文獻(xiàn)報(bào)道基本相符[2]。冠狀動(dòng)脈閉塞引起心肌缺血可導(dǎo)致氧自由基增多，進(jìn)而導(dǎo)致心肌細(xì)胞結(jié)構(gòu)改變和代謝紊亂，同時(shí)也會(huì)引起胞質(zhì)和線粒體內(nèi)鈣超載，進(jìn)一步加重細(xì)胞膜降解[11]。Iwakura等[12]研究發(fā)現(xiàn)，由缺血相關(guān)損傷導(dǎo)致的冠狀動(dòng)脈微血管栓塞中，缺血時(shí)間起重要作用。通過(guò)觀察發(fā)現(xiàn)，冠狀動(dòng)脈閉塞90 min后再灌注，導(dǎo)致嚴(yán)重的毛細(xì)血管損傷，內(nèi)皮細(xì)胞突起以致阻塞毛細(xì)血管腔，血管外紅細(xì)胞也將堵塞內(nèi)皮細(xì)胞間隙[13]。當(dāng)持續(xù)缺血時(shí)間超過(guò)3 h，再灌注可加重缺血相關(guān)損傷[14]。缺血時(shí)間延長(zhǎng)在致死性再灌注損傷（再灌注引起的心肌壞死）和冠狀動(dòng)脈微血管栓塞中尤為關(guān)鍵[15]。冠狀動(dòng)脈栓塞通過(guò)引起中性粒細(xì)胞和血小板聚集，又產(chǎn)生大量收縮血管物質(zhì)和炎癥介質(zhì)。

另外本研究亦提示，中性粒細(xì)胞百分比升高更容易發(fā)生無(wú)復(fù)流。冠狀動(dòng)脈硬化是炎癥反應(yīng)的過(guò)程，而炎癥標(biāo)志物可以作為預(yù)測(cè)臨床結(jié)局的因子[16]。在冠狀動(dòng)脈疾病患者中，炎癥因子的增加可能加劇病情[17]。受損心肌區(qū)域首先出現(xiàn)的是中性粒細(xì)胞，促凝物質(zhì)由局部的白細(xì)胞釋放，這增加了氧化損傷和蛋白水解損傷[18]。此外，中性粒細(xì)胞浸潤(rùn)可增加血液粘滯度，增加無(wú)復(fù)流發(fā)生。

總之，無(wú)復(fù)流現(xiàn)象有著復(fù)雜的病理生理學(xué)特點(diǎn)，可能還與患者的臨床特征、影像學(xué)特征以及手術(shù)方式有關(guān)。本研究存在以下不足：①未觀察評(píng)價(jià)心肌灌注的其他影像學(xué)特征，如心肌顯像積分和TIMI幀計(jì)數(shù)等；②入選的病例數(shù)仍然偏少，且入選病例行PCI并非同一術(shù)者；③本研究是單中心、小樣本的回顧性研究，因此仍需大樣本、多中心、前瞻性、隨機(jī)臨床試驗(yàn)來(lái)證實(shí)本研究結(jié)論的可靠性。

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本文編輯：姚雪莉

Risk factors of no-reflow during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction

YUAN Chi*, KE Yong-sheng, KE Ke.*Department of Cardiovascular Diseases, Yijishan Hospital, Wannan Medical College, Wuhu 241000, China.

Objective To analyze the relevant risk factors of no-reflow during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods STEMI patients undergone primary PCI were chosen (n=166, male 139, female 27, aged from 36 to 91 and average age=63.10±11.96) from the Department of Cardiovascular Diseases of the First Affiliated Yijishan Hospital of Wannan Medical College from May 2012 to Dec. 2015. All patients were divided into normal perfusion group (n=142) and no-reflow group (n=24) according to the outcomes of angiography after vascular mechanical patency. The general clinical materials including ischemia time and complicating basic diseases were collected. The samples of vein blood were collected at the time of hospitalization and after hospital admission for detecting neutrophil percentage, platelet count (PLT) and low-density lipoprotein-cholesterol (LDL-C), and diseased vascular diameter and target lesion length were measured. Results The ischemia time and neutrophil percentage were all higher in no-reflow group than those in normal perfusion group (all P＜0.01). The results of regression analysis showed that ischemia time＞6 h (OR=1.578, 95%CI: 1.245～2.000) and neutrophil percentage＞80.0% (OR=3.405, 95%CI: 1.027～11.293) were risk factors of no-reflow after primary PCI. Conclusion In the patients with acute STEMI undergone primary PCI, ischemia time is longer and neutrophil percentage increases significantly and probability of no-reflow will be higher.

Acute ST-segment elevation myocardial infarction; Primary percutaneous coronary intervention; No-reflow

R541.4

A

1674-4055(2016)11-1354-03

1241000 蕪湖,皖南醫(yī)學(xué)院弋磯山醫(yī)院心血管內(nèi)科;2102249 北京,中國(guó)人民解放軍裝備學(xué)院昌平士官學(xué)校門(mén)診部

柯永勝,E-mail:keyongsheng@163.com

10.3969/j.issn.1674-4055.2016.11.20