An Experimental Study On Protective Effects Of Monophosphoryl Lipid A Preconditioning With Cold Crystalloid Cardioplegia To Immature Myocardium

Objective:The study was desined to study the protective effects and possible mechanism of monophosphoryl lipid A(MLA) preconditioning with cold crystalloid cardioplegia to immature myocardial ischemia-reperfusion injury.Methods:To use the isolated working heart model,isolated hearts have been 120 minutes and 15℃cold ischemia,and then 37℃and 60 minutes reperfusion.24 pure breed New Zealand neonatal rabits,age 3-4 weeks,weight 430±30g,were available.They were divided into 3 groups of 8.Specific group as follows:Control group(CON),which perfused the heart with cold CrystaUoid cardioplegia only before the ischemic.Schemia preconditioning group(IPC):Giving 5 minutesof single global ischemia and 5 minutes of Mechanical preconditioning before the ischemic,and then perfused the heart with cold crystalloid cardioplegia.Preconditioning group(MLA):To give the MLA preconditioning at 24 hours before ischemia,and then perfusedthe heart with cold crystalloid cardioplegia.The basic values before the ischemia and the recovery rate of ardiac function after the ischemia were observed.The observations were HR,SAP,LVSP,+dp/dt,-dp/dt,CSF,and the indexes in the coronary artery effluent including CK,LDH,MDA,SOD,Endothelial function(NO,ET),and myocardial ATP content,and also consists of morphological changes of myocardial with light microscope,ultrastructural changes with electron microscope.We used TUNEL to assay the myocardial apoptosis cells,and calculate the apoptotic index(AI).Results:1.Before the ischemic,there were no significant differences between IPC and CON on HR,SAP,LVSP,±dp/dt and CSF(P>0.05),while there were significant differences between MLA and IPC,ON(p<0.05).The values of CK and CON were similar among the three groups(P>0.05).There were no significant differences between IPC and CON on MDA,SOD,ET and NO(P>0.05),while there were significant differences between MLA and IPC,CON(p<0.05).2.In the period of reperfusion,the recovery rate of cardiac function at each time points after ischemia in the IPC and MLA were both higher than CON, respectively(p<0.05).And the difference were evident particularly at 60 minutes after reperfusion between MLA and IPC(p<0.05).The values of HR was similar among the three groups(P>0.05).The value of CK,LDH,MDA and ET in the coronary artery effluent in MLA and IPC were lower and the value of SOD and NO were higher than those in CON (p<0.05).Compared with IPC,MLA had a marked increase in SOD and NO(p<0.05) andsignificant reduction in CK,LDH,MDA,ET.3.The content of ATP in myocardial tissue in IPC and MLA were both higher than that in CON.And there were significant differences between MLA and IPC of ATP value(p<0.05).4.Population distribution position of AI value in myocardial tissue were higher in MLA,and latter in CON.And there were no signifcant differences among the three groups of AI value(P<0.01).5.To observe the injury of morphological changes under light microscope and ultrastructural changes with electron microscope,IPC and MLA were less injuried than that in CON,especially in MLA.Conclutions:1.The pretective effects on immature myocardial ischemia-rePerfusion injury of MLA preconditioning and IPC combining with cold crystal myocardial protective solution were both better than cold crystal myocardial protective solution only.2.The pretective effects on immature myocardial ischemia-reperfusion injury of MLA preconditioning combining with cold crystal myocardial protective solution was better than that of IPC with cold crystal myocardial protective solution.