Nicorandil超极化心脏停搏液对未成熟兔心肌的保护作用  

The study of the protective effects on immature rabbit myocardia with hyperpolarization cardioplegia drug Nicorandil

作　　者：王玺胜[1] 汪发久[1] 季强[1] 蔡建志[1] 孙益峰[1] 梅运清[1] 

机构地区：[1]同济大学附属同济医院胸心血管外科,上海200065

出　　处：《同济大学学报（医学版）》2010年第2期32-37,共6页Journal of Tongji University(Medical Science)

摘　　要：目的观察不同浓度ATP敏感性钾通道开放剂尼可地尔(Nicorandil)超极化心脏停搏对未成熟兔心肌的保护作用,以提高婴幼儿手术中心肌保护效果。方法将32颗离体新西兰幼兔心脏随机分为4组:实验Ⅰ组、实验Ⅱ组、实验Ⅲ组、实验Ⅳ组,每组8颗。建立Langendorff离体灌注心脏模型,以KHB液体灌注30 min后达平衡状态,转为工作模型。实验Ⅰ组间断灌注KHB液;实验Ⅱ组、实验Ⅲ组、实验Ⅳ组分别灌注ST.ThomasⅡ号停搏液、ST.ThomasⅡ号停搏液+Nicorandil 10μmol/L、ST.ThomasⅡ号停搏液+Nicorandil 100μmol/L;每15 min重复1次,共灌注2次;然后用KHB液体再灌注30 min,实验时间总共90 min。实验开始、第60 min及结束时各收集一次血流动力学指标:左室发展压(left ventricular developed pressure,LVDP)、左室舒张末压(left ventricular end-diastolicpressure,LVEDP)、左室内压最大变化率(rate of rise of left ventricular pressure,±dp/dt)及心肌酶指标:乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)。实验标本做病理切片观察心肌结构变化。结果实验Ⅲ组、实验Ⅳ组与实验Ⅰ组相比,血流动力学指标及心肌酶指标明显改善(P<0.01),实验Ⅲ组、实验Ⅳ组与实验Ⅱ组相比,血流动力学指标及心肌酶指标明显改善(P<0.05),实验Ⅱ组与实验Ⅰ组相比各项指标改善(P<0.05),实验Ⅲ组的心功能恢复弱于实验Ⅳ组,但差异无统计学意义(P>0.05)。镜下实验Ⅰ组、实验Ⅱ组心肌损伤重,实验Ⅲ组、实验Ⅳ组损伤较轻。结论单纯的高钾停跳液可以为未成熟兔心肌提供一定的保护作用。Nicorandil超极化心脏停跳液可以为未成熟兔心肌提供保护作用,且其保护作用明显优于单纯的高钾停跳液;但在实验范围内浓度的差别引起的保护作用差异不明显。Objective To evaluate the protective effects of hyperpolarization cardioplegia drug Nicorandil on immature rabbit myocardia at different concentrations in hope of improving the outcome in infant cardiosurgery. Methods Thirty-two hearts isolated from immature New Zealand rabbits were randomly assigned into 4 groups with 8 rabbits each. Animals in group Ⅰ suffered no cardioplegia as control; animals from group Ⅱ , Ⅰ and Ⅳ were all induced to have cardioplegia by adminstrating high potassium. Nicorandil was given to animals in group Ⅲ and Ⅳ at concentrations of either 10 μmol/L or 100 μmol/L. By means of Langendorff apparatus,the isolated heart in thermostat was perfused with KHB first for 30 min at 37 ℃ to reach for working status. Subsequently, isolated hearts in group Ⅰ, Ⅱ ,Ⅲ and Ⅳ were perfused by respective solutions by 20～25 ml in volume within 30 min. At the beginning,60th rain and the end of the experiment,the hemodynamic indexes including left ventricular developed pressure（LVDP）,left ventricular end-diastolic pressure （LVEDP） ,rate of left ventricular pressure rise（＋dp/dt） and myocardial enzymes like lactate dehydrogenase（LDH） and creatine kinase（CK） were measured. The pathologic changes of heart samples were also examined. Results In group m and group ]V ,the indexes of hemodynamic parameters and myocardial enzyme activities were significantly better than that in control animals （group Ⅰ ,P〈0.01） and in animals without Nicorandil treatment（group Ⅱ ,P〈0.05）. The indexes of group Ⅱ was better than group Ⅰ （P〈0.05）. Under light microscopy, the damage of heart muscle in group Ⅲ and group Ⅳ was less severe than that in group Ⅰ and group Ⅱ . Conclusion Hyperpolarization cardioplegia Nicorandil can give significant protective effects to myocardia in immature rabbit at a dose-independent fashion. Meanwhile single injection of high potassium cardioplegia can also give some protective effects.

关 键 词：尼可地尔 钾通道 未成熟心肌 心肌保护 

分 类 号：R655[医药卫生—外科学]