·論著·

陳章強，戴軍，姚民，洪浪，王洪

作者單位：330006江西省南昌市，江西省人民醫(yī)院心內(nèi)科(陳章強，洪浪，王洪)；中國醫(yī)學(xué)科學(xué)院阜外心血管病醫(yī)院(戴軍，姚民)

通信作者：陳章強，330006江西省南昌市，江西省人民醫(yī)院心內(nèi)科；E-mail：chenzq888@163.com

【摘要】目的比較地爾硫和硝普鈉在改善急性冠脈綜合征(ACS)患者經(jīng)皮冠狀動脈介入(PCI)治療中無復(fù)流現(xiàn)象的效果。方法選取2008年1月—2014年6月于江西省人民醫(yī)院接受PCI治療且術(shù)中出現(xiàn)無復(fù)流現(xiàn)象的ACS患者80例為研究對象，采用隨機數(shù)字表法將患者分為地爾硫組(40例)和硝普鈉組(40例)。兩組于PCI術(shù)中經(jīng)微導(dǎo)管冠狀動脈靶病變遠端2 s內(nèi)“彈丸式”快速分別給予地爾硫、硝普鈉200～600 μg，分別于給藥后10、20 min后復(fù)查冠狀動脈造影，評價心肌梗死溶栓治療(TIMI)血流分級和校正的TIMI血流幀數(shù)(CTFC)，同時記錄給藥前及給藥后10、20 min有創(chuàng)血壓及心率的變化。分別于PCI術(shù)前及術(shù)后7、30 d記錄左心室收縮末內(nèi)徑(LVESD)、左心室舒張末內(nèi)徑(LVEDD)及左心室射血分數(shù)(LVEF)。于PCI術(shù)前及術(shù)后7、30 d測定N末端B型腦鈉肽前體(NT-proBNP)及細胞因子超敏C反應(yīng)蛋白(hs-CRP)、白介素6(IL-6)及細胞間黏附分子-1(ICAM-1)水平。記錄兩組術(shù)后30 d內(nèi)主要心血管事件(再發(fā)心絞痛、再發(fā)急性心肌梗死及心力衰竭發(fā)作)和其他心血管事件(惡性心律失常及猝死)的發(fā)生情況。結(jié)果不同藥物對TIMI血流分級、CTFC、收縮壓、舒張壓及心率的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組用藥后10、20 min TIMI血流分級、CTFC與用藥前比較，差異有統(tǒng)計學(xué)意義(P<0.05)。不同藥物對LVESD、LVEDD、LVEF的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組術(shù)后30 d LVESD、LVEDD及LVEF與術(shù)前比較，差異有統(tǒng)計學(xué)意義(P<0.05)。不同藥物對NT-proBNP、hs-CRP、IL-6及ICAM-1的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組術(shù)后7、30 d NT-proBNP、hs-CRP、IL-6、ICAM-1水平均低于術(shù)前，差異有統(tǒng)計學(xué)意義(P<0.01)。兩組術(shù)后30 d內(nèi)主要心血管事件及其他心血管事件發(fā)生率比較，差異均無統(tǒng)計學(xué)意義(P>0.05)。結(jié)論地爾硫和硝普鈉均能夠有效改善PCI術(shù)中TIMI血流分級及CTFC，降低炎性因子和NT-proBNP水平，改善心功能，兩者改善無復(fù)流現(xiàn)象的效果相當(dāng)。

【關(guān)鍵詞】急性冠脈綜合征；經(jīng)皮冠狀動脈介入治療；無復(fù)流現(xiàn)象；地爾硫；硝普鈉；療效比較研究

【中圖分類號】R 542.2

收稿日期：(2015-05-07；修回日期：2015-11-08)

Chen ZQ， Dai J， Yao M,et al.Effects of diltiazem and sodium nitroprusside on alleviating no-reflow phenomenon in patients with acute coronary syndrome during percutaneous coronary intervention[J].Chinese General Practice，2015，18(35)：4283-4287.

Effects of Diltiazem and Sodium Nitroprusside on Alleviating No-reflow Phenomenon in Patients With Acute Coronary Syndrome During Percutaneous Coronary InterventionCHENZhang-qiang，DAIJun，YAOMin,etal.DepartmentofCardiology，JiangxiProvincialPeople′sHospital,Nanchang330006,China

Abstract【】ObjectiveTo make a comparison between diltiazem and sodium nitroprusside in alleviating no-flow phenomenon in patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI).MethodsWe enrolled 80 ACS patients who had no-flow phenomenon during PCI undertaken in Jiangxi Provincial People′s Hospital from January 2008 to June 2014.Using random number table method,the patients were divided into two groups:diltiazem group (group A,n=40) and sodium nitroprusside group (group B,n=40).Group A was given diltiazem 200-600 μg by pellet injection from microcatheter selective coronary to far-end target lesions in two seconds,group B was given sodium nitroprusside 200-600 μg in the same way.Coronary arteriography was retaken 10 minutes and 20 minutes after administration.Thrombolysis in Myocardial Infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were evaluated.Invasive blood pressure and heart rate were recorded before administration and 10 minutes and 20 minutes after administration.LVESD,LVEDD and LVEF were recorded before PCI and 7 days and 30 days after PCI.The levels of NT-proBNP,hs-CRP,IL-6 and ICAM-1 were recorded before PCI and 7 days and 30 days after PCI.The incidence rates of major cardiovascular events (re-angina,re-myocardial infarction and heart failure) and other cardiovascular events (malignant arrhythmia and sudden death) were recorded.ResultsThe two medicines were not significantly different (P>0.05) in the influence on TIMI flow grade,CTFC,systolic pressure,diastolic pressure and heart rate.TIMI flow grade and CTFC of the two groups at 10 minutes and 20 minutes after administration were significantly different from those before administration (P<0.05).The two medicines were not significantly different (P>0.05) in the influence on LVESD,LVEDD and LVEF.The levels of LVESD,LVEDD and LVEF of the two groups on 30 days after administration were significantly different from those before administration (P<0.05).The two medicines were not significantly different (P>0.05) in the influence on NT-proBNP,hs-CRP,IL-6 and ICAM-1.The levels of NT-proBNP,hs-CRP,IL-6 and ICAM-1 of the two groups on 7 days and 30 days after administration were significantly different from those before administration (P<0.05).The two groups were not significantly(P>0.05) different in the incidence rates of major cardiovascular events and other cardiovascular events.ConclusionDiltiazem and sodium nitroprusside can effectively improve TIMI flow grade and CTFC,reduce the levels of inflammatory factor and NT-proBNP and improve cardiac function.The two medicines have equally good effect on alleviating on-flow pheonmenon.

【Key words】Acute coronary syndrome；Percutaneous coronary intervention；No-reflow phenomenon；Diltiazem；Nitroprusside；Comparative effectiveness research

1資料與方法

1.2方法

1.2.1基線資料包括患者性別、年齡、吸煙史、合并糖尿病、ACS類型及入院時血壓、血脂水平〔三酰甘油(TG)、總膽固醇(TC)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)〕。

1.2.3心功能測定分別于PCI術(shù)前及術(shù)后7、30 d復(fù)查心臟彩超(美國惠利普公司Agilent 5500型)，記錄左心室收縮末內(nèi)徑(LVESD)、左心室舒張末內(nèi)徑(LVEDD)及左心室射血分數(shù)(LVEF)。

1.2.4N末端B型腦鈉肽前體(NT-proBNP)及細胞因子水平的測定分別于PCI術(shù)前及術(shù)后7、30 d測定NT-proBNP及細胞因子超敏C反應(yīng)蛋白(hs-CRP)、白介素6(IL-6)及細胞間黏附分子-1(ICAM-1)水平。NT-proBNP的測定采用膠體金標法，試劑盒購自丹麥Radiometer Medical ApS公司，變異系數(shù)為0.5%；hs-CRP的測定采用免疫散射比濁法，試劑盒購自美國德靈公司，按照試劑盒說明書嚴格進行操作,變異系數(shù)為1.5%；IL-6和ICAM-1的測定采用酶聯(lián)免疫吸附試驗(ELISA)，按試劑盒說明書嚴格進行操作,變異系數(shù)為1.2%。

1.2.5預(yù)后記錄兩組術(shù)后30 d內(nèi)主要心血管事件(再發(fā)心絞痛、再發(fā)急性心肌梗死及心力衰竭發(fā)作)和其他心血管事件(惡性心律失常及猝死)的發(fā)生情況。

2結(jié)果

2.1基線資料比較兩組性別、年齡、吸煙、糖尿病、ACS類型、收縮壓、舒張壓、TG、TC、HDL-C及LDL-C比較，差異均無統(tǒng)計學(xué)意義(P>0.05，見表1)。

2.2兩組用藥前后TIMI血流、血壓及心率變化不同藥物與時間對TIMI血流分級、CTFC、收縮壓、舒張壓及心率的影響無交互作用(P>0.05)。不同藥物對TIMI血流分級、CTFC、收縮壓、舒張壓及心率的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組用藥后10、20 min TIMI血流分級、CTFC與用藥前比較，差異有統(tǒng)計學(xué)意義(P<0.05,見表2)。

2.3兩組患者心臟結(jié)構(gòu)及心功能比較不同藥物與時間對LVESD、LVEDD、LVEF的影響無交互作用(P>0.05)。不同藥物對LVESD、LVEDD、LVEF的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組術(shù)后30 d LVESD、LVEDD及LVEF與術(shù)前比較，差異有統(tǒng)計學(xué)意義(P<0.05,見表3)。

2.4兩組NT-proBNP、細胞因子水平比較不同藥物與時間對NT-proBNP、hs-CRP、IL-6及ICAM-1的影響無交互作用(P>0.05)。不同藥物對NT-proBNP、hs-CRP、IL-6及ICAM-1的影響比較，差異無統(tǒng)計學(xué)意義(P>0.05)。兩組術(shù)后7、30 d NT-proBNP、hs-CRP、IL-6、ICAM-1水平均低于術(shù)前，差異有統(tǒng)計學(xué)意義(P<0.01，見表4)。

2.5預(yù)后兩組術(shù)后30 d內(nèi)主要心血管事件及其他心血管事件發(fā)生率比較，差異均無統(tǒng)計學(xué)意義(P>0.05,見表5)。

表1　兩組患者一般資料比較

注：ACS=急性冠脈綜合征，AMI=急性心肌梗死，UAP=不穩(wěn)定型心絞痛，TG=三酰甘油，TC=總膽固醇，HDL-C=高密度脂蛋白膽固醇，LDL-C=低密度脂蛋白膽固醇；a為χ2值

表2　兩組患者血流、血壓及心率比較 ±s)

注：TIMI=心肌梗死溶栓治療，CTFC=校正的TIMI血流幀數(shù)；與同組用藥前比較，aP<0.05

表3　兩組患者心臟結(jié)構(gòu)及心功能比較 ±s)

注：LVESD=左心室收縮末內(nèi)徑，LVEDD=左心室舒張末內(nèi)徑，LVEF=左心室射血分數(shù)；與同組術(shù)前比較，aP<0.05

表4　兩組NT-proBNP和細胞因子水平比較 ±s)

注：NT-proBNP=N末端B型腦鈉肽前體，hs-CRP=超敏C反應(yīng)蛋白，IL-6=白介素6，ICAM-1=細胞間黏附分子-1；與同組術(shù)前比較，aP<0.05

表5兩組術(shù)后30 d心血管事件發(fā)生率比較〔n(%)〕

Table 5Comparison of the incidence rates of cardiovascular events between the two groups

組別例數(shù)主要心血管事件其他心血管事件地爾硫卓艸組404(10.0)1(2.5)硝普鈉組404(10.0)1(2.5)χ2值<0.01<0.01P值>0.05>0.05

3討論

1972年，Tambe等[18]首次報道急性心肌梗死(AMI)患者急診PCI術(shù)中出現(xiàn)慢血流現(xiàn)象,此后隨著冠心病患病率的升高及PCI的廣泛推廣，該現(xiàn)象已被介入醫(yī)生所熟悉。由于無復(fù)流現(xiàn)象不能實現(xiàn)心肌組織的有效灌注，成為PCI術(shù)后近期和遠期預(yù)后不良的危險因素[3]。無復(fù)流現(xiàn)象發(fā)生機制復(fù)雜，尚未完全闡明，有學(xué)者提出可能與微血管損傷、微血管栓塞、血管痙攣、氧化應(yīng)激、血小板激活及白細胞聚集等有關(guān)[8,19]。炎性反應(yīng)是介導(dǎo)動脈斑塊破裂導(dǎo)致AMI的重要原因，也是導(dǎo)致無復(fù)流現(xiàn)象的重要機制之一[20]。本研究結(jié)果發(fā)現(xiàn)，兩組患者PCI術(shù)后7、30 d，與炎性反應(yīng)有關(guān)的細胞因子hs-CRP、IL-6、ICAM-1表達水平均低于術(shù)前。血清NT-proBNP是主要由心室肌細胞合成的心源性神經(jīng)激素，具有拮抗腎素-血管緊張素-醛固酮系統(tǒng)、利尿排鈉、擴張血管等作用，其水平升高常見于心室容量負荷、室壁壓力增高及心肌細胞受損等。本研究顯示，兩組患者術(shù)前NT-proBNP水平明顯增高，可能與交感神經(jīng)和腎素-血管緊張素-醛固酮系統(tǒng)激活，心室肌細胞的應(yīng)激及室壁張力增高有關(guān)。

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(本文編輯：吳立波)