卡立泊来德复合心脏停跳液对兔未成熟心肌的保护作用

Cardioprotective effects of cariporide as an adjunct in different cardioplegic solutions:an experiment with rabbits

目的比较选择性钠氢离子交换阻断剂卡立泊来德(Cariporide)联合不同心脏停跳液(St.Thomas 液与 HTK 液)对未成熟心肌缺血/再灌注损伤的保护作用。方法 32只新西兰幼兔(2～3周龄),建立 Langendorff 离体心脏灌注模型后,随机分为4组,每组8只:对照组(St 组,St.Thomas液)、HTK 组(HTK 液)、St+C 组(St.Thomas 液中添加 Cariporide)和 HTK+C 组(HTK 液中添加Cariporide)。所有心脏均30℃全心缺血120 min,37℃KH 液再灌注60 min。记录心功能参数:左室发展压(LVDP)、左室最大收缩变化率(+dp/dt_(max))、左室最大舒张变化率(-dp/dt_(max))及冠脉流量(CF);测定冠脉流出液中磷酸肌酸激酶同工酶(CK-MB)、心肌三磷酸腺苷(ATP)、丙二醛(MDA)、心肌细胞内钙(iCa)及心肌含水量(WC)。结果 HTK 组 LVDP、+dp/dt_(max)、-dp/dt_(max)、CF 恢复率及ATP 含量均明显高于 St 组(P<0.05),CK-MB、MDA、WC 和 iCa 明显低于 St 组(P<0.05);St+C 组、HTK+C 组各指标分别优于 St 组、HTK 组,且 HTK+C 组各指标则优于 St+C 组;而 St+C 组与 HTK组比较显示,St+C 组-dp/dt_(max)、CF 恢复率和 ATP 高于 HTK 组(P<0.05),而 MDA 高于 HTK 组(P<0.05),其余指标两组差异无统计学意义(P>0.05)。结论 Cariporide 能提高 St.Thomas 液及HTK 液对未成熟心肌缺血再灌注损伤的保护作用。

Objective To investigate the cardioprotective effects of cariporide as an adjunct in different cardioplegic solutions. Methods The hearts of 32 young New Zealand rabbits were isolated, hung on the Langendorff perfusion apparatus, arrested with 4℃ cardioplegic solutions to cause cardiac ischemia for 120 min, reperfused with 37℃ Krebs-Henseleit solution, and randomly divided into 4 equal groups： St. Thomas cardioplegic solution group （perfused with St. Thomas cardioplegic solution every 30 min ）, histidine-tryptophane-ketoglutarate （HTK） cardioplegic solution group （perfused with HTK solution, St. Thomas solution ＋ cariporide （St ＋ C ） group （perfused with St. Thomas cardioplegic solution plus cariporide） , and HTK solution plus cariporide （HTK ＋ C） group （perfused with HTK cardioplegic solution plus cariporide）. Multichannel physiological record instrument was used to record the left ventricular functions： left ventricular diastolic pressure （LVDP）, maximum change rate of left ventricular systolic pressure rise and fall （ ＋ dp/dtmax ）, maximum change rate of left ventricular diastolic pressure rise and fall （-dp/dtmax）, and coronary flow （CF）. Automatic biochemical analyzer was used to measure the creatine kinase （CK）-MB, Then the level of ATP in the cardiac muscle ceils was detected by high pressure liquid chromatography, the content of malonyldialdehyde （MDA） was detect by sulfur barbituric acid method. The calcium content （iCa） was measured by atomic absorption spectrophotometry. And the mypcardial water content （WC） was measured too. Results The LVDP, ＋ dp/dtmax, - dp/dtmax, CF recovery rate, and ATP content of the HTK group were all significantly higher than those of the St. Thomas group （ all P 〈 0. 05 ）, and the CK-MB, MDA, WC, and iCa of the HTK group were all significantly lower than those of the St. Thomas group （ all P 〈 0.05 ）. The ATP level of the HTK ＋ C group was significantly higher than thoseof the HTK and St ＋ C groups （both P 〈 0. 05 ）, and the CK-MB, WC, MDA, and iCa of the HTK ＋ C group were all lower than those of the HTK and St ＋ C groups （ all P 〈 0.05）. The MDA level of the St ＋ C group was significantly higher than that of the HTK group, and the ATP of the St ＋ C group was significantly lower than that of the HTK group （ both P 〈 0.05 ）, however, there was no significant differences in CK- MB, WC, and iCa between these 2 groups （ all P 〉 0. 05 ）. Conclusion Cariporide enhances the cardioprotective effects of the St. Thomas and HTK cardioplegic solutions in immature myocardium.