尼可地尔联合替罗非班对急性心肌梗死患者急诊PCI术后心肌微循环和心功能短期预后的影响

Effects of combination therapy of tirofiban and nicorandil on cardiac function and myocardial microcirculation in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention

目的探讨急诊PCI术中及术后冠脉及静脉内给予尼可地尔和替罗非班对急性心肌梗死患者PCI术后心肌微循环和心功能短期预后的影响。方法连续入选行急诊PCI的急性心肌梗死患者120例,随机分为联合组、替罗非班组和对照组各40例。联合组和替罗非班组均于PCI术中冠脉内给予负荷量替罗非班10μg/kg,随后予替罗非班0.15μg/(kg·min)持续静脉滴注至PCI术后48 h;联合组在应用替罗非班基础上PCI术中冠脉内给予尼可地尔负荷量0.06 mg/kg,随后予尼可地尔2 mg/h持续静点48 h。术后3组均予常规冠心病Ⅱ级预防药物治疗。统计3组PCI术后冠脉TIMI血流3级比率及校正的冠脉TIMI血流帧数,并在术后6,10,14,18,24和48 h测定血清肌酸激酶(CK)、肌酸激酶同工酶(CKMB)及超氧化物歧化酶(SOD)、内皮素(ET)和高敏C反应蛋白(hs-CRP)以找出其中峰值浓度,术后24 h及4周后测定血浆N-末端脑钠肽前体(NT-pro BNP)水平及行超声心动图测定左室舒张末内径(LVEDD)、左室收缩末内径(LVESD)和左室射血分数(LVEF)。结果联合组和替罗非班组术后冠脉TIMI血流3级比率均明显高于对照组(P均<0.05),PCI术后冠脉校正的TIMI血流帧数及48 h内CK、CK-MB峰值浓度均明显低于对照组(P均<0.05),但联合组和替罗非班组比较差异均无统计学意义(P均>0.05);48 h内联合组SOD峰值浓度明显高于其他2组(P均<0.05),ET和hs-CRP峰值浓度均明显低于其他2组(P均<0.05),替罗非班组和对照组比较差异均无统计学意义(P均>0.05)。术后24 h,3组血浆NT-pro BNP水平和LVEDD、LVESD、LVEF比较差异均无统计学意义(P均>0.05);术后4周,联合组血浆NT-pro BNP水平及LVESD、LVEDD均明显低于其他2组(P均<0.05),LVEF均明显高于其他2组(P均<0.05),而替罗非班组与对照组比较差异均无统计学意义(P均>0.05)。结论尼可地尔联合替罗非班不仅可通过抗血小板和抗血栓作用明显改善心肌微循环,而且可通过扩张冠状动脉微循环血管和抗氧化、抗炎及改善冠状动脉微循环血管内皮功能等减轻心肌再灌注损伤,两种药物联合应用可以明显减少急性心肌梗死急诊PCI术后心肌损伤和坏死,可改善心功能短期预后。

Objective It is to evaluate the effects of combination therapy of tirofiban and nicorandil on cardiac function and myocardial microcirculation in patients with acute ST segment elevation myocardial infarction（ STEMI） after percutaneous coronary intervention（ PCI）. Methods 40 patients with STEMI admitted to Aviation General Hospital from September 2012 to May 2015 were selected randomly into contrast group and 40 cases into tirofiban observation group and 40 cases into tirofiban and nicorandil observation group. Loading dose of tirofiban by bolus drop. Nicorandil（ 0. 06 mg / kg） was dropped into coronary artery during PCI and（ 2 mg / h） used in nicorandil and tirofiban group for 48 hs after PCI. The rate of TIMI 3 grade and corrected TIMI frame count（ CTFC） was counted in three groups. Tirofiban（ 10 μg / kg） was injected into intracoronary by bolus according to weight of patients in tirofiban and combination groups during PCI. After PCI tirofiban [0. 15 μg /（ kg·min） ] was used for 48 hs Concentrations of serum CK,CK-MB,Endotheiin（ ET）,superoxide dismutase（ SOD） and high sensitive C-reactive protein（ hs-CRP） were tested at 6 h,10 h,14 h,18 h,24 h and 48 h after PCI for finding out the peak level. Amino terminal-pro brain natriuretic peptide（ N-pro BNP） was checked and Echocardiography was done at 24 h and 4 weeks.Results The rate of TIMI 3 grade was higher in two observation groups than one in contrast group（ P〈0. 05）. Serum peak levels of CK,CK-MB and CTFC were lower after therapy in two observation groups than ones in contrast group（ P〈0. 05）,no differences between two observation groups（ P〉0. 05）. Though serum peak levels of ET and hs-CRP were lower and SOD was higher in nicorandil and tirofiban group than ones in tirofiban and contrast groups（ P〈0. 05）,no differences between tirofiban and contrast groups（ P〉0. 05）. NT-pro BNP and value of LVEDD,LVESD and LVEF were no different among three groups at 24 h after PCI. In nicorandil and tirofiban group N-pro BNP and value of LVEDD,LVESD was lower and value of LVEF was higher than ones in contrast group 4 weeks after PCI（ P〈0. 05）. Though value of LVEF was increasing trend in tirofiban group than one in contrast group,no significant change was found in two groups（ P〉0. 05）. Conclusion Nicorandil and tirofiban treatments may improve myocardial blood supply by ablating microcirculation and anti-thrombus but also may decrease myocardial ischemia-reperfusion injury and improve endothelial function of coronary artery by anti-inflammatory and antioxidant. Combination therapy Nicorandil and tirofiban might decrease myocardium injury and enhance cardiac function.