Protective Effect Of Levosimendan And Ulinastain On Myocardium To Isolated Immature Rabbit Hearts

Objective:Levosimendan is a novel calcium sensitizer that improves central haemodynamics and symptoms of patients with chronic heart failure and myocardial stunning and cardiogenic shock, but the protective effects of Levosimendan on ischemia-reperfusion(I/R) injury to the immature hearts were not reported. The urinary trypsin inhibitor (Ulinastatin) has been used to inhibit inflammatory response with substantial clinical treatment, but the protective effects of Ulinastatin on ischemia-reperfusion(I/R) injury to the immature hearts were not reported. Our objective is to evaluate the myocardial protective effects of Levosimendan and ulinastain and Levosimendan in combination with ulinastain against ischemia-reperfusion(I/R) injury to the isolated immature rabbit hearts and investigate its mechanisms.Methods:Forty New Zealand long-ear white immature rabbits (age 3-4Week) of both sexes weighing 300-400g were divided into 4 groups randomly. Their hearts were immediately removed and mounted on Langendorff apparatus and perfused with oxygenated K-H solution at 37℃.40 isolated hearts were randomized into 4 groups with 10 hearts in each group of hearts underwent 30 min reperfusion after 30 min global myocardial ischemia; the hearts were perfused with K-H solution in groupⅠ(C); with Ulinastain+ K-H solution in groupⅡ(U); with Levosimendan+ K-H solution in groupⅢ(L); with Ulinastain+ Levosimendan+K-H solution in group IV (UL). (1) heart rate (HR),left ventricular pressure(LVP) and LVdp/dtmax were monitored; (2) coronary flow (CF) was collected and measured; (3) effluent from coronary sinus was collected at time of ischemia/reperfusion for determination of TNF-a,IL-6,CK,cTnl concentration.Results:(1)The HR, LVP, LVdp/dtMax, CF were significantly better in group UL, U, L than in the C groups (P<0.01). (2)The LVP, LVdp/dtmax at 10-30 min of reperfusion were significantly better in group UL than in the other 3 groups(P<0.01 or 0.05). (3)The CK,cTnl concentration in the effluent from coronary sinus at 0,10,30 min of reperfusion was significantly lower in group UL than in the other 3 groups.Conclusion:Levosimendan may reduce immature myocardial reperfusion injury, and Ulinastain may reduce immature myocardial reperfusion injury. The immature myocardial protective effects of Levosimendan in combination with Ulinastain was better than that of Levosimendan and Ulinastain alone.