The Effects Of Ketamine Combined With Magnesium Sulfate On The Isolated Rat Heart Suffering From Ischemia And Rperfusion Injury

THE EFFECTS OF DIFFERENT DENSITY OF KETAMINE COMBINED WITH MAGNESIUM SULFATE(KMS) ON ISOLATED RAT HEART FUNCTION SUFFERING FROM ISCHEMIA AND REPERFUSION INJURYObjective: To investigate the effecs of KMS on isolated rat heart suffering from ischemia and reperfusion injury as well as the relationship between the effects and density.Methods: 80 mature male SD rat were randomly divided into 8 groups(n=10): normal control group(NC), ischemia reperfusion group(IR), group KMS-LL(Ketamine 0.001 mmol/L+magnesium Sulfate 1.5mmol/L + IR), group KMS-LH(Ketamine 0.001mmol/L+magnesium sulfate 3.0 mmol/L+IR), group KMS-ML(Ketamine 0.01mmol/L+magnesium sulfate 1.5mmol/L+IR), group KMS-MH(ketamine 0.01mmol/L+magnesium sulfate 3.0mmol/L+IR), group KMS-HL(ketamine 0.1mmol/L+ magnesium sulfate1.5mmol/L+IR),and group KMS-HH(ketamine 0.1mmol/L+magnesium Sulfate 3.0mmol/L+IR). Group NC: perfused 190min with K-H fluid without ischemia and reperfusion. Group IR:perfused 30min with fluid K-H, then ischemia reperfusion injury was induced by 40min globle ischemia and 120min reperfusion. Group KMS: perfused 20min with K-H fluid, 10min before ischemia and during the whole reperfusion perfused with fluid K-H containing different density of ketamine and magnesium sulfate which has been mentioned before. we record the alteration of HR, LVSP, LVEDP,±dp/dtmax and CF of each group at different perfusion point, then evaluate the effects of KMS on heart function and analysis the relationship between the effects and the density.Results: compared with group NC,each KMS group can inhibit the decline of HR,LVDP,±dp/dtmax,CF and the increase of LVEDP caused by ischemia and reperfusion , and group KMS-LL may be more efficient than KMS-HH, the difference between them is significant(P<0.05).Conclusion: KMS shows the protective effect on heart function injured ischemia reperfusion in some degree ,especially the group of 0.001mmol/L ketamine combined with 1.5 mmol/L magnesium sulfate;and the protective effect turn out to be a trend of decline with the increase of density of KMS.PARTⅡThe EXPRESSION OF NMDAR IN RAT MYOCARDIUM Objective: To testify the expression of NMDA in myocardium and to search for a new method to cure the myocardial ischemia reperfusion injury.Methods: Take the left ventricle from the normal mature male SD rat , and detect the mRNA expression of NMDAR1, NMDAR2A, NMDAR2B by RT-PCR.Result: The mRNA expression of NMDAR1 was detected in rat myocardium, but neither the mRNA of NR2A nor NR2B was found .Conclusion: NMDAR1 is present in the myocardium of mature male SD rat, but it's function is still unknown,we supposed that it may be the target of excitability material making effects in heart, and it may have a role in myocardial ischemical reperfusion injury. The biological acativity of NMDAR1 in heart may be related to the homozygotic type of NMDAR1-NMDAR1. The antagonist of NMDAR may be a new direction and strategy in studying the drugs to protect heart from ischemia reperfusion injury in future.PARTⅢTHE STUDY OF THE PROTECTIVE MECHANISM OF KMS ON THE ISOLATED RAT HEART INJURED BY ISCHEMIA AND REPERFUSIONObjective: To investigate the injury of NMDA to normal myocardial and to study the protective mechanism of KMS on myocardial injury induced by ischemia reperfusion and NMDA. Methods: 50 mature male SD rats were divided into 5 groups randomly(n=10), namely: group NC, IR, KMS(Ketamine 0.001 mmol/L + magnesium Sulfate 1.5mmol/L) ,NMDA and KMS+NMDA.Using the model of langendorff-perfusion in isolated heart, by investigating the alteration of heart function ,activity of LDH,CK and the contents of cTn-I in the coronary flow, the contents of NO and activity of NOS in heart tissue, as well as the apoptosis in heart tissue and the change of myocardial ultrastructure, we evaluate the injury of NMDA and the ischemia reperfusion to isolated rat heart, and study the relationship between NO,NOS,and EAA with injury as well as the protective mechanism of KMS.Results:The injury induced by 1mmol/L NMDA to heart is similar to that induced by ischemia reperfusion, Such as the decline of HR, LVDP,±dp/dtmax, CF and the increase of LVEDP and LDH, CK, cTn-I in CF, NO and NOS in heart tissue, apoptosis index in heart tissue, as well as the damage of myocardial ultrastructure,compared with group NC , the difference is significant ( P<0.01 ) . KMS (ketamine 0.001mmol/L+magnesium sulfate 1.5mmol/L)can attenuate these injurys.As far as each observation index was concerned, the difference between group KMS and group IR,NMDA is significant(P<0.01).Conclusion: EAA was also detected in heart tissue and may have the relationship with ischemia reperfusion injury , the excitotoxicity of EAA may also occur in heart disease. KMS may preserve heart by inhibiting the release of NO, NOS and EAA,thus inhibit the apoptosis of myocardial cell.And this mechanism may be related to inhibiting the activation of NMDAR.