钙增敏剂左西孟旦对大鼠离体心脏缺血-再灌注损伤的影响  

The effects of levosimendan on myocardial ischemia-reperfusion injury in isolated rat hearts

作　　者：李新巧[1] 刘金东[2] 曾因明[2] 

机构地区：[1]徐州医学院第二附属医院麻醉科,徐州市221006 [2]江苏省麻醉医学研究所

出　　处：《临床麻醉学杂志》2013年第4期400-404,共5页Journal of Clinical Anesthesiology

摘　　要：目的观察新型强心药钙增敏剂左西孟旦对大鼠离体心脏缺血-再灌注后心功能及心肌损伤的影响。方法雄性SD大鼠32只,随机均分为四组。在Langendorff灌注装置上建立离体心脏缺血-再灌注损伤模型。再灌注期间K-H液分别加入左西孟旦0.3μmol/L(L组)、多巴酚丁胺0.1μmol/L(D组)及无水乙醇0.6mmol/L(S组),C组为单纯K-H液。记录平衡灌注末(T1)、再灌注10min(T2)、20min(T3)、30min(T4)、60min(T5)、120min(T6)时心功能指标:左室舒张末压(LVEDP)、左室发展压(LVDP)、左室内压变化最大速率(±dp/dtmax)、HR及冠脉流量(CF)。在T1、再灌注5min(T1a)、T2～T5时用化学比色法测定各组冠脉流出液中乳酸脱氢酶(LDH)和肌酸磷酸激酶(CK)含量。灌注结束后,用TUNEL法测定心肌细胞凋亡指数(AI),用TTC染色法测定心肌梗死面积(MIS)。结果 T2～T6时L组LVEDP、±dp/dtmax明显低于其它三组(P<0.05),LVDP、CF明显高于其它三组(P<0.05);D组HR明显快于其它三组(P<0.05)。T2～T4时D组LDH和CK含量显著高于其它三组(P<0.01)。D组心肌AI和MIS均明显高于其它三组(P<0.05),而L组明显低于C组(P<0.05)。结论与传统强心药多巴酚丁胺比较,左西孟旦更好地改善大鼠离体心脏缺血-再灌注后心功能,且不进一步加重心肌损伤。Objective To observe the effects of new cardiac calcium sensitizer levosimendan on cardiac function and myocardial ischemia-reperfusion injury in isolated rat hearts. Methods Thirty- two male isolated SD rats hearts were randomly divided into 4 groups （n= 8） .. control group（group C）, levosimendan group （group L）, dobutamine group （group D） and absolute alcohol group （group S）. These hearts were per{used with a Langendorff apparatus for 20 rain at 37~ C for equilibrium. Ischemia-reperfusion injury was produced after 25-rain global ischemia and 120 min reperfusion. Rats were reperfused with K-H perfusate （group C）, the K-H perfusate containing 0. 3 t^mol/L levosimendan（group L）, 0. 1 t^mol/L dobutamine（group D）, or 0. 6 mmol/L absolute alcohol （group S）for 120 min. The indexes of cardiac mechanical function including LVEDP, LVDP, ~dp/dt^as well as HR and corollary flow（CF） were measured at end of per{using（T1 ）, 10 min（T2 ） ,20 min（Ta ）, 30 rain（T4 ）,60 min（Ts ）, 120 rain（T6 ） after reperfusion. The contents of LDH and CK in coronary effluent were measured with chemistry colorimetry at T1, reperfusion 5 min （T1,）, and T2-T5. Myocardial apoptotic index（AI）and myocardial infarct size （MIS）were measured with TUNEL and TIC staining method respectively. Results The LVEDP and ±dp/dtmax were significantly lower and LVDP,CF were significantly higher in group L at T2-T6 during reperfusion than the other three groups （P〈0.05）. HR was higher in group D at T2-T6 than the other three groups. Levels of LDH and CK at T2-T4 as well as AI and MIS after reperfusion in group D were significantly higher than the other three groups（P〈0.05 or P〈0.01）, whereas AI and MIS in group L were lower than those in group C （P〈0.05）. Conclusion Compared with traditional inotropics dobutamine, levosimendan has better improvement on cardiac function in isolated rat heart after ischemia-reperfusion without exacerbation to the myocardial injury.

关 键 词：左西孟旦 多巴酚丁胺 缺血-再灌注损伤 心肌 

分 类 号：R965[医药卫生—药理学]