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Cardioprotective Effects Of Levosimendan On Myocardial Ischemia/reperfusion Injury In Isolated Rat Hearts

Posted on:2008-02-14Degree:MasterType:Thesis
Country:ChinaCandidate:H F JiangFull Text:PDF
GTID:2144360215489323Subject:Anesthesia
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Objective To investigate the effects of Levosimendan on ischemia/reperfusion myocardium and its mechanism in isolated rat hearts. Methods Female wistar rats weighing 250~300g, were anesthetized and heparinized. The hearts were rapidly removed after thoracotomy and mounted on modified Langendorff apparatus. After a 10-min equilibration period, the hearts were randomly divided into 4 groups with 8 animals in each group: ischemia/reperfusion (I/R) group, Levo 30nmol·L-1 (L1) group, Levo 300nmol·L-1 (L2) group and Levo+Gliben (L+G) group. During equilibration, the left ventricle was fitted with a balloon inflated to a diastolic pressure of 4 to 6 mmHg. In I/R group ,the hearts were perfused with K-H solution for 20 mAn. In L1 and L2 group, perfused with 30nmol·L-1 Lero and 300nmol·L-1 hero before ischemia respectively. In L+G group, perfused with 300nmol·L-1 Levosimendan and 10μmol·L-1 Glibenclamide for 20 man before ischemia. Then, all the hearts were subjected to no-flow global normothermic ischemia for 30 min, following ischemia, hearts were reperfused with the same solution for 30 min. Hemodynamic parameters and coronary flow were recorded before ischemia, at 10th min, 20th man and 30th man after reperfusion .CK and LDH were measured before ischemia and at 30th man after reperfusion. Tissue at heart apexes was retended after experiment. The concentration of both ATP and Ca2+ in myocardium were calculated .Results : (1) There were no significant differences of HR,LVDP,+dp/dtmax—dp/dtmax,CF among groups before ischemia (P>0.05);(2)Post-ischemia, the HR,LVDP,+dp/dtmax,—dp/dtmax,CF in each group tend to decrease, but HR,LVDP,+dp/dtmax,— dp/dtmax,CF were significantly improved in L2 group(P<0.05).However, there were no significant differences between the others(P>0.05);(3)There were no statistic differences of CK and LDH among groups before ischemia (P>0.05) ;(4)After reperfusion, both CK and LDH were lower in L2 group than that of the others(P<0.01, P<0.05);No statistic differences among the others(P>0.05);(5)ATP content in L2 group was significant higher than that of the others(P<0.01),however, there were no significant differences between the others(P>0.05);(6)After reperfusion, the concentration of calcium ion in myocardium of L2 group was significantly lower than that of the others(P<0.01),no statistic differences among others (P>0.05).Conclusion 300nmol·L-1Levosimendan can protect myocardium from ischemia—reperfusion injury by openning the KATP channel in isolated rat hearts.
Keywords/Search Tags:Levosimendan, Glibenclamide, ischemia /reperfusion, cardioprotective effect, KATP channel
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