| ObjectiveTo investigate the effects of Ranolazine on myocardial ischemia/reperfusion injury in isolated rat hearts and its mechanism,by modified Langendorff apparatus.MethodsChose 32 male Wistar rats,weighing 220～250g,dividied into four groups randomly(n=8):Ischemia/Reperfusion group(I/R group),Ran 10μmol·L-1(R10) group,Ran20μmol·L-1(R20)group,Ran10μmol·L-1and 200μmol·L-1H2O2 (R+H)group.After the rats were anesthetized with urethane(1.5g/kg)and heparinized inter-peritoneally,the hearts were rapidily removed from the thoracic cavity and connected to Langendorff apparatus.The left ventricle was fitted with a balloon full of 37℃saline to inform a diastolic pressure ranged from 5 to 10mmHg. After 15min equilibration,all hearts were subjected to a no-flow global normothermic ischemia for 30min.Following ischemia,I/R group was reperfused with K-H solution for 60min,and R10,R20,R+H group,were perfused with 10μmol·L-1Ran,20μmol·L-1Ran,10μmol·L-1Ran and 200μmol·L-1H2O2 for 60min respectively. Hemodynamic parameters were recorded before ischemia,at the 15th min,30th min,45th min,60th min during reperfusion.The coronary flow was also taken before ischemia and at the 60th min to measure LDH and CK.Tissue at heart apexes was retented after experiment used to detected ATP and Ca2+content.Results1.The influence on hemodynamic There were no significant differences of HR,LVDP,+dp/dtmax,-dp/dtmaxamong groups before hearts arrested(P＞0.05).After reperfusion,HR,LVDP,+dp/dtmax,-dp/dtmaxin each group had the tendency to decrease,LVDP,+dp/dtmax,-dp/dtmaxin R10 and R20 group were better than I/R and R+H group(P＜0.05),and R20 group was better than R10 group(P＜0.05),no statistic differences between the I/R and R+H group(P＞0.05).There were no statistic differences of HR among four groups(P＞0.05).2.The influence on the myocardial leak enzyme There were no statistic differences of LDH and CK among groups before the hearts stopped(P＞0.05).After reperfusion,both LDH and CK had the tendency to increase,and they were lower in R10 and R20 group than I/R and R+H group(P＜0.05),no statistic differences between the R10 and R20 group(P＞0.05);no statistic differences between the I/R and R+H group(P＞0.05).3.The influence on ATP and Calcium ion ATP content in R10 and R20 group were both higher than I/R and R+H group(P＜0.05),and ATP content in R20 was higher than that in R10(P＜0.05),no statistic differences between the I/R and R+H group(P＞0.05).The content of Calcium ion in myocardium of R10 and R20 group were both lower than the I/R and R+H group(P＜0.05),and R20 was lower than R10(P＜0.05),no statistic differences between the group I/R and R+H(P＞0.05).ConclusionRanolazine can protect myocardium from ischemia-reperfusion injury. Ranolazine can improve the contraction force of ischemia/reperfusion myocardium, increase the content of ATP and decrease the content of Calcium ion,and lighten the myocardium injury,depended on the dose in certain concentration. |
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