替罗非班联用前列地尔对急诊经皮冠脉介入治疗术后心肌梗死患者心肌再灌注和心功能短期预后的影响

Effects of combination therapy of Tirofiban and Alprostadil on short term prognosis of cardiac function and myocardial ischemia-reperfusion in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention

目的探讨急诊经皮冠脉介入治疗(PCI)术前至术后联合应用替罗非班和前列地尔对急性ST段抬高型心肌梗死(STEMI)患者PCI术后心肌再灌注和心功能短期预后的影响。方法入选行急诊PCI的STEMI患者75例,随机分为常规治疗组(n=25)、替罗非班治疗组(n=25)和替罗非班联合前列地尔治疗组(联合治疗组)(n=25);替罗非班治疗组和联合治疗组均于PCI术前静脉滴注替罗非班,并于PCI术中冠脉内给予负荷量10μg/kg,随后0.15μg/(kg.min)持续静脉滴注至PCI术后48 h;联合治疗组在应用替罗非班基础上PCI术前开始静脉滴注前列地尔,并于PCI术中冠脉内给予10μg,随后静脉滴注(20μg/次,2次/d)至PCI术后48 h。术后三组均常规冠心病药物治疗。三组在术后6、10、14、18、24、48 h测定血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肿瘤坏死因子α(TNF-α)、内皮素(ET)及高敏C反应蛋白(hs-CRP)以找出其中峰值浓度,于术后24 h和14 d测定血浆N-末端脑钠肽前体(NT-proBNP)浓度和左心室射血分数(LVEF)。结果联合治疗组和替罗非班治疗组术后CK、CK-MB、LDH峰值浓度[(1298±346)、(1344±357)、(217±86)U/L和(235±104)、(1786±356)、(1883±389)U/L)]明显低于常规治疗组[(1896±453)、(426±128)、(2334±454)U/L)](P<0.05),替罗非班治疗组和联合治疗组比较差异无统计学意义(P>0.05);联合治疗组TNF-α、ET和hs-CRP峰值浓度[(17.69±2.39)、(85.4±11.4)ng/L和(4.13±1.56)mg/L)]明显低于替罗非班治疗组和常规治疗组[(23.36±3.14)ng/L和(25.68±3.21)ng/L、(118.3±13.9)ng/L和(121.6±14.8)ng/L、(5.98±2.07)mg/L和(6.32±2.22)mg/L](P<0.05),替罗非班治疗组和常规治疗组比较差异无统计学意义(P>0.05)。三组24 h血浆NT-proBNP浓度[(1325±323)、(1286±316)、(1269±299)ng/L]和LVEF[(44.6±6.7)%、(45.4±6.3)%和(45.8±6.1)%]无明显差异,联合治疗组14 d血浆NT-proBNP浓度明显低于常规治疗组[(236±112)ng/L比(456±208)ng/L],LVEF值明显高于常规治疗组[(54.3±5.2)%比(46.4±5.8)%],差异有统计学意义(P<0.05)。替罗非班治疗组与常规治疗组比较,LVEF值[(48.8±5.4)%比(46.4±5.8)%]有增高趋势但差异无统计学意义(P>0.05)。结论急诊PCI中替罗非班联合前列地尔治疗不仅可通过抗血小板和抗血栓明显改善心肌微循环,而且可通过扩张冠状动脉、抗炎及改善冠脉血管内皮功能等减轻心肌再灌注损伤,联合应用两种药物较单用替罗非班可以减少心肌坏死,可改善心功能短期预后。

Objective To explore the effects of combination therapy of Tirofiban and Alprostadil on short-term progno sis of cardiac function and myocardial ischemia-reperfusion in patients with acute ST segment elevation myocardial in farction（STEMI） after percutaneous coronary intervention（PCI）.Methods 75 patients with STEMI verified by clinical features were investigated consecutively and randomly divided into routine therapy group（n = 25） and Tirofiban therapy group（n = 25） and combination therapy of Tirofiban and Alprostadil group（combination therapy group）（n = 25）.Tirofiban was used by intravenous drop before PCI and loading dose of Tirofiban（10 μg/kg） was injected into intracoronary by bolus according to weight of patients in Tirofiban and combination therapy group during PCI.After PCI Tirofiban [0.15 μg/（kg.min）] was used for 48 h incessantly by intravenous drop.On the base of therapy of Tirofiban Alprostadil（10 μg） was injected into intracoronary during PCI and Alprostadil（once 20 μg,bid） was used in combination therapy group from before PCI to 48 h after PCI.Regular therapy of drugs was adopted in three groups.Concen trations of serum CK,CK-MB,LDH,Endotheiin（ET）,tumor necrosis factor α（TNF-α） and high sensitive C-reactive protein（hs-CRP） were examined at 6,10,14,18,24 h and 48 h after PCI for finding out the peak level of every testing index.Concentration of plasma amino terminal-pro brain natriuretic peptide（N-proBNP） was examined and echocardiography was performed at 24 h and 14 days after therapy.Results Serum peak levels of CK,CK-MB,LDH were lower after therapy in combination therapy group and Tirofiban therapy group [（1298 ±346）,（217 ±86）,（1786±356） U/L and（1344±357）,（235±104）,（1883±389） U/L] than ones in routine therapy group [（1896 ±453）,（426± 128）,（2334±454） U/L]（P ＆lt; 0.05）,while there were no significant differences between Tirofiban and combination ther apy group（P ＆gt; 0.05）.Though serum peak levels of ET,TNF-α and hs-CRP were lower in combination therapy group [（17.69±2.39） ng/L,（85.4 ±11.4） ng/L,（4.13 ±1.56） mg/L] than ones in Tirofiban therapy group and routine therapy group [（23.36 ±3.14） ng/L and（25.68 ±3.21） ng/L,（118.3 ±13.9） ng/L and（121.6 ±14.8） ng/L,（5.98 ±2.07） mg/L and（6.32±2.22） mg/L]（P ＆lt; 0.05）,there were no significant differences between Tirofiban therapy group and routine thera py group（P ＆gt; 0.05）.Concentration of plasma N-proBNP [（1325 ±323）,（1286 ±316）,（1269 ±299） ng/L）] and value of LVEF [（44.6±6.7）%,（45.4±6.3）% and（45.8±6.1）%] were not different among three groups at 24 h after PCI.In combination therapy group concentration of plasma N-proBNP [（236±112） ng/L] was lower and value of LVEF [（54.3±5.2%）] was higher than ones [（456±208） ng/L and（46.4±5.8）%] in routine therapy group in 14 d after PCI（P ＆lt; 0.05）.Though value of LVEF was higher in Tirofiban therapy group [（48.8±5.4）%] than one in routine therapy group [（46.4±5.8）%],no significant change was found in two groups（P ＆gt; 0.05）.Conclusion Combination therapy of Tirofiban and Alprostadil in patients with acute PCI not only increases myocardial microcirculation by anti-platelet and anti-thrombus but also decreases myocardial ischemia-reperfusion injuries by dilating coronary artery and improving endothelial function of coronary artery and anti-inflammatory.Combination therapy may be reduce myocardial necrosis and im prove short-term prognosis of cardiac function.