| Objective To investiagate the effects of levosimendan(Levo) in St.ThomasⅡ(STH-2) cardioplegic solution on isolated rat heart, approach the relationship between the effects and opening the ATP-sensitive potassium channel.Methods 32 healthy majoritied male wastar rats, weighing about 250-300g, were randomly divided into 4 groups (n=8 in each), including L0, L1,L2,LG.The rats were anesthetized with 3% pentobarbital sodium 30 mg/kg inter-peritoneally and heparinized with heparin sodium 500 IU/kg.After thoracotomy the heart was removed and mounted on modified Langendorff apparatus,and kept the hearts in 37℃. Each heart was perfused with Kerbs-Henseleit Bicarbonate buffer (KHB) for 30 min.Then group L0 was perfused with STH-2 cardioplegia solution;group L1,L2 and LG were perfused with STH-2 cardioplegia solution containing Levo 0.03μmol/L(L1), Levo 0.3μmol/L(L2) and Levo 0.03μmol/L+Glibenclamide(Glib) 10μmol/L(LG). The isolated hearts were fist perfused with different cardioplegic solutions for 120min and then with KHB for 30 min.Heamodynamic parameters:Heart rate(HR), Left ventricular developed pressure(LVDP),+differential pressure timemaxium (+dp/dtmax) and -differential pressure timemaxium(-dp/dtmax) were recorded at baseline, and at 10min,20 min and 30 min of reperfusion. Creatine Kinase(CK)and Lactate Dehydrogenase (LDH)were measured at baseline, and at 10min,20 min and 30 min of reperfusion. Tissue arround apexes, weighing about 200 mg was cutted after the experiment. Concentrations of Malondialdehyde (MDA),Superoxide Dismutase (SOD), Adenosine triphosphate(ATP)and the content of water in myocardium were measuered.Results (1) Influence on hemodynamics There were no statistical significances of HR, LVDP,+dp/dtmax,-dp/dtmax before ischemia among four groups (P>0.05). After ischemia-reperfusion, HR,LVDP,+dp/dtmax and -dp/dtmax tends to decrease in each group (P<0.05). Compared with group L0, the hemodynamic parameters were much higher in group L2,there was no statistical significance in group L1 and LG (P>0.05); Compared with group L1, the hemodynamic parameters were much higher in group L2 (P＜0.01 or P<0.05). there was no statistical significance in group LG (P>0.05); Compared with group L2, the hemodynamic parameters were much lower in group L2 (P<0.05 or P<0.01).(2) Influence on myocardial enzymes leak There were no statistical significances of CK and LDH among four groups before ischemia (P>0.05). After reperfusion, CK and LDH tends to decrease in each group (P<0.05). Compared with group LO, the CK and LDH activities significant dcrease in group L1 and L2(P<0.05 or P<0.01), there was no statistical significance in group LG(P>0.05); Compared with group L1,the CK and LDH activities significant dcrease in group L2 (P<0.05 or P<0.01), there was no statistical significance in group LG(P>0.05);Compared with group L2, the CK and LDH activities kept higher level in group LG(P<0.05 or P<0.01).(3) Influence on the content of ATP,MDA, water and the activity of SOD After reperfusion, compared with group L0, the content of MDA dcrease and the SOD activity kept higher level in group L1 (P<0.05),the content of MDA significant dcrease when the content of ATP and the SOD activity kept relatively higher level in group L2 (P<0.01), there was no statistical significance in group LG(.P>0.05);Compared with group L1,the content of MDA significant dcrease and the content of ATP and the SOD activity kept relatively higher level in group L2 (P<0.01), there was no statistical significance in group LG(P>0.05);Compared with group L2, the content of MDA significant increase and the content of ATP and the SOD activity kept relatively lower level in group LG (P＜0.01). There was no statistical significances of the content of water in myocardium(P>0.05).Conclusion Levo added into STH-2 cardioplegic solution can protect myocardium from ischemia-reperfusion injury. The possible mechnism is promoting opening the ATP-sensitive potassium channel.The effect relate to the dose of Levo. |
PDF Full Text Request