卡立泊来德对鼠移植供心的保护效果

Protective effect of cariporide on isolated donor heart for transplantation in rats

目的通过离体心脏灌流模型(Langendorff),评价卡立泊来德(Cariporide)对离体鼠移植供心的保护效果。方法 48只雄性Wistar大鼠随机分为四组。对照组两组:HTK(Histidine-Tryptophan-Ketoglurate Solution)8h、12h组,实验组(Cariporide组)两组:HTK+Cariporide 20μmol/L,8h、12h组。切取鼠供心后即悬挂在Langendorff上灌注,测定血流动力学基础值。分别用两种器官保存液灌注离体鼠心后置于各自的冷心肌保护液(4℃)中保存8h、12h,恢复灌注后再次测定血流动力学指标和冠状动脉流量,留取标本分别测定心肌水含量、心肌酶漏出量、心肌细胞ATP含量,观察心肌细胞超微结构变化。结果在冷缺血8h后,与对照组相比,实验组的平均左室发展压(LVDP)及心肌ATP含量均增高,磷酸肌酸激酶同工酶(CK-MB)漏出量减少,但差异无统计学意义。在冷缺血12h后,与HTK组相比,卡立泊来德组LVDP均显著升高[(98.37±16.34)mmHg、(43.21±14.33)mmHg,(P<0.01)](1mmHg=0.133kPa);CK-MB漏出量明显减少[(4.373±1.489)IU/L、(34.23±3.328)IU/L,(P<0.01)];心肌ATP含量明显增多[(34.32±1.87)μg/g、(17.92±1.47)μg/g,(P<0.01)]。结论 Cariporide对离体鼠供心具有较好的保护效果,并可延长供心的低温保存时间。

Objective To assess the protective effect of cariporide on isolated donor heart for transplantation in rats through Langendorff. Methods Forty-eight male Wistar rats were randomly divided into control group which was further divided into 8h and 12h histidine-tryptophan-ketoghirate（HTK） solution groups and experiment group which was further divided into 8h and 12h 20 μ mol/L cariporide±HTK groups. The isolated donor hearts removed from rats were perfused in Langendorff with their basic hemodynamic values assayed, and then preserved in cold cardiac muscle protective solutions at 4 ℃ for 8h and 12h, respectively. Their hemodynamic parameters and blood flow in coronary artery were detected after reperfusion. Water content, release of CK-MB from cardiac muscle, and APT level in cardiac ceils were measured. Changes in ultra-microstructure of cardiac ceils were observed. Results The mean left ventricular developed pressure（LVDP） and ATP level in cardiac muscle were significantly higher in experiment group than in control group 8h after ischemia induced by hypothermia（P〈0.05）. The release of CK-MB from cardiac muscle was decreased, but no significant difference was observed in it between the 2 groups. The mean LVDP was significantly higher, the release of CK-MB from cardiac muscle was significantly less, and the ATP level in cardiac muscle was significantly higher in cariporide group than in HTK group 12h after ischemia induced by hypothermia（（98.37 ± 16.34）mmHg vs （43.21 ± 14.33）mmHg, （4.373 ± 1.489）IU/L vs （34.23 ± 3.328）IU/L, （34.32 ± 1.87） μ g/g vs （17.92 ± 1.47） μ g/g, （P〈0.01））. Conclusion Cariporide can protect isolated donor rat hearts and prolong their cold preservation time.