Relationship Between The Expression Of Cardiac Specific MiRNA And The Myocardial Protective Effect Of Levosimendan

Objective:To investigate the effect of levosimendan on the expression of cardiac specific miRNA in patients undergoing selective mitral valve replacement with cardiopulmonary bypass(CPB),to study the relationship between the expression of cardiac specific miRNA and the myocardial protective effect of levosimendan.Methods:30 adult patients undergoing selective mitral valve replacement were randomized to receive either 24μg/kg levosimendan(L group,n=15)or placebo(C group,n=15).LS or placebo were administrated intravenously after anesthesia induction and before CPB.Plasma CK-MB,cTnI,H-FABP and IMA level were measured after anesthesia induction(T0),and fifteen minutes(T1),two hours(T2),twelve hours(T3)after aortic de-clamping respectively.A piece of atrial tissue was removed 30 min after aortic de-clamping from each patient and was used to measured the cardiac specific miRNA by RT-q PCR.The following haemodynanic parameters were measured during observational period: mean arterial pressure,heart rate and central venous pressure.The time of CPB,postoperative mechanical ventilation,length of ICU stay were recorded down,as well as the ECG and the rate of auto-rebeat of heart.Results:1.There was no significant difference between two groups in gender,age,body mass index,preoperative left ventricular ejection fraction,CPB time,aortic de-clamping time,and length of ICU stay(P>0.05).The postoperative mechanical ventilation time in group L was significantly lower than that in group C(P<0.05);the rate of auto-rebeat of heart in group L was higher than that in group C(P<0.05).2.The differences of HR,MAP,and CVP between the two groups during the perioperative period were statistically insignificant(P>0.05).No malignant arrhythmia occurred in both groups.It is safe and fe asible to use 24μg/kg LS after anesthesia induction and before CPB.3.CK-MB,cTnI,H-FABP and IMA: CK-MB and cTnI:Compared with T0,plasma concentration of CK-MB and cTnI in both groups in creased significantly at T3(P<0.05).There was no significant difference in the concentration of CK-MB and cTnI between these two groups from T0 to T2(P>0.05).The concentration of CK-MB and cTnI in group L was lower than that in group C at T3(P<0.05).H-FABP: Compared with T0,plasma concentration of H-FABP in the two groups increased significantly from time T1 to T3(P<0.05).There was no significant difference in the concentration of H-FABP between groups(P>0.05).The concentration of H-FABP in group L was lower than that in group C at T1-T3,and the difference was statistically significant(P<0.05).IMA: Compared with T0,IMA plasma concentration in two groups increased significantly from T1 to T2(P<0.05).There was no significant difference in the concentration of IMA between groups T0 and T3(P>0.05).At the time of T1 to T2,the concentration of IMA in group L was lower than that of group C.The difference was statistically significant(P<0.05).4.Cardiac specific miRNA: The expression of miRNA-1 in group L was significantly lower than that in group C(P<0.05).The expression of miRNA-133 and miRNA-499 in group L were significantly increased compared with group C.These differenceswere statistically significant(P<0.05).Conclusions: 1.Levosimendan can reduce the release of cTnI,CK-MB,IMA,and H-FABP in cardiomyocytes in patients undergoing mitral valve replacement with CPB,and decrease the perioperative myocardial injury.Improve the rate of auto-rebeat of heart,shorten post operative mechanical ventilation time.2.For cardiac specific miRNA,levosimendan can down-regulate the expression of miRNA-1 and up-regulate the expression of miRNA-133,-499,miRNA may ploy an important role in the myocardial protective effect of levosimendanthroughreducing myocardial ischemia-reperfusion injury.