| Background: Although the medical facilities and methods were well developed in recent years, ischemic heart disease is still the most important cause of death in developed countries and more and more people in developing countries were threatened by this disease. Most investigation outcome shows that: myocardial ischemia/reperfusion injury is depending not only on the time of ischemia but also on the degree of reperfusion injury. So, to explore an effective to prevent myocardial ischemia/reperfusion injury is the aim of medical worker. In recent year, "postconditioning" have become a new focus to investigate to reduce ischemia/reperfusion injury. Most researches have proved that ischemia and pharmacology postconditioning are effective way to reduce ischemia/reperfusion injury. Lidocaine is commonly used local anesthetics of amide derivatives and a drug to treat ventricular arrhythmia. There are so many researches to investigate that if lidocaine can reduce myocardial ischemia/reperfusion injury and its mechanism, but they get different outcome. There haven't research to investigate if lidocaine postconditioning can reduce myocardial ischemia/reperfusion injury, in this research, we investigate that if lidocaine postcondition and infusion during reperfusion can reduce ischemia/reperfusion injury and its possible mechanism.Objectives: (1) To investigate whether lidocaine could induce the postconditioning against acute myocardial ischemia/reperfusion injury in SD rats; (2) To know the difference effect of different dose of lidocaine on acute myocardial ischemia/reperfusion injury in SD rats; (3) To investigate the effect of lidocaine on myocyte apoptosis, bcl-2, bax and Cx43 of reperfusion myocardial tissue; (4) By use the special mitoKATP channel blocker 5-HD to investigate if the protection effect of lidocaine is mediated by mitoKATP channel.Methods: This study consists of the following three parts. Part one: Myocardial protection of lidocaine on acute ischemic reperfusion. Healthy male SD rats were studied. All animals were anesthetized with pentobarbital sodium 50mg/kg i.p. and mechnical wentilation was maintained. The rats were randomly assigned into 5 groups and subjected to 30min occlusion of the left anterior descending coronary artery followed by a period of 120min reperfusion in vivo. Group ischemia/reperfusion (group I/R) without any other intervention; Group L1 received intravenous administration of a single dose of lidocaine 2mg/kg before reperfusion; Group L2 received intravenous administration of a single dose of lidocaine 5mg/kg before reperfusion; Group CL1 received a dose of 2mg/kg lidocaine just before reperfusion followed by continuous infusion by the rate of 100ug/kg/min during the first 60min of reperfusion; Group CL2 received a dose of 2mg/kg lidocaine just before reperfusion followed by continuous infusion by the rate of 200ug/kg/min during the first 60min of reperfusion. Heart rate, mean artery pressure and lead II electrocardiogram were continuously monitored. HR, MAP, RPP and arrhythmia was recorded; To determine plasma concentration of MDA and activity of SOD, arterial blood samples were abtained before ischemia and at the end of experiment; After 120min reperfusion, rats hearts were removed for myocardial infarct size measurement and examine the tissue with optical microscope. Part two: Influence of lidocaine on myocyte apoptosis, bcl-2, bax and connexion43 of the reperfusion tissue. The healthy male SD rats were anesthetized with pentobarbital sodium 50mg/kg i.p. and mechanical ventilation was maintained. The rats were randomly assigned into 3 groups: Group C, group I/R and group CL2. All the hearts in group C were received sham operation without ischemia and reperfusion procedure and no other intervention; The hearts in group I/R and group CL2 received 30min LAD occlusion followed 120min reperfusion. Group CL2 received a dose of 2mg/kg lidocaine just before reperfusion follow by continuous infusion by the rate of 200ug/kg/min during the first 60min of reperfusion while group I/R without other intervention. At the end of experiment, all hearts were removed and reperfusion tissue were separated for detect myocyte apoptosis, bcl-2, bax and Cx43. Part three: The possible signal mechanism which mediats lidocaine's myocardial protection effect. The healthy male SD rats were anesthetized with pentobarbital sodium 50mg/kg i.p. andmechanical ventilation was maintained. The rats were randomly assignedinto 4 groups: group I/R, group 5-HD, group CL2 and group Cl2+5-HD. Thehearts in all groups endured 30min LAD occlusion followed 120minreperfusion. We infusion 5mg/kg of 5-HD to all rats in group 5-HD andgroup CL2 + 5-HD before reperfusion. And a dose of 2mg lidocainefollowed continuous infusion by the rate of 200ug/kg/min for 60min afterreperfusion was used for rats in group CL2 and group CL2 + 5-HD.Hemodynamics and infart size was recorded to judge the degree of injury.Results: (1) Both single dose and continuous infusion of lidocaine used inour experiment can maintain more stable hemodynamics duringreperfusion, increases SOD sctivity and reduce the density of MDA inblood plasma, compared with which in group I/R, P<0.05 , and therate of severe arrhythmic is lower in all lidocaine groups(compared withthat in group I/R, P<0.05); (2) Single dose of lidocaine used beforereperfusion can't reduce myocardial infarct size (compare AN/AAR ofgroup L1, L2 with group I/R, P>0.05); Continue injection of lidocaineduring reperfusion can reduce mayocardial infarct size: AN/AAR in groupCL1 and CL2 is 44±5 % and 36±5 % respectively, compared withAN/AAR in I/R (56±7%) , P<0.05 or P<0.01. And the effect oflidocaine to reduces infart size is dose depending: AN/AAR in CL2 issmaller than that in group CL1, P<0.05; (3) Continuous infusion of lidocaine during reperfusion can reduce neutrophil infiltration, increase the ratio of bcl-2/bax and reduce myocyte apoptosis (apoptosis index in group I/R was 14±5.2% and was 6.0±3.3% in group CL2, it was lower than that in group I/R, P<0.01); (4) Ischemia/reperfusion can make the Cx43 degradation (OD in group C was higher than that in group I/R, P< 0.01) Continuous infusion of lidocaine during reperfusion can prevent the degradation of Cx43 induced by ischemia/reperfusion injury (OD in group CL2 was higher than that in group I/R, P<0.01) ; (5) 5-HD can abolish the protection effect of lidocaine to reduce reperfusion injury: AN/AAR in group CL2+5-HD is same with that in group I/R, P>0.05, is bigger than that in group CL2, P<0.05.Conclusions: (1) Single dose of lidocaine used before reperfusion or continue injection during reperfusion can reduces reperfusion arrhythmia; (2) Single dose of lidocaine used before reperfusion can't reduce myocardial infart size; (3) Lidocaine have the effect to prevent rat acute myocardial reperfusion injury; (4) The protection of lidocaine on rat acute myocardial reperfusion injury is related to reduces oxidative stress, reduces neutrophil infiltration, reduces myocyte apoptosis and to prevents Cx43 degradation during reperfusion ; (5) mitoKATP channel mediates the protection effect of lidocaine on rat acute myocardial reperfusion injury.
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