心肌缺血预处理PPT课件.ppt

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1、EARLYSIGNALINGPATHWAYINHEARTPROTECTIONBYISCHEMICPRECONDITIONINGIschemicpreconditioning(PC)isthephenomenondescribingprotectionoftheheartagainstreperfusioninjuryfollowingprolongedischemia,byvirtueofpriorshortepisode(orepisodes)ofischemiaandreperfusion.Ananalogousphenomenonofcardiacprotectionagains

2、treperfusioninjurybypre-administrationofadrugiscalleddrug-inducedPC.Wehavedevelopedafamilyofdrugsthatcandoit.IschemiaR1R2Stabilization10minReperfusion20minPc1Pc2Pc3R3TheSystem:IsolatedratheartTheprocedure:Threeepisodesof2’globalischemiaseparatedby3’reperfusionPCTwowindowsofprotectionbyischemicPC

3、havebeenidentified:1–3hoursfollowingPC,and24hourfollowingPC.Weworkwiththeisolatedratheart,andwillfocusonthefirstwindow.CardiacFunctionwithoutandwithPChasbeenstudied.Belowthefollowingparametersarepresented:DP=PSP-EDP+dP/dtEDPotherparametersnotshownDevelopedPressure(DP)(%ofpre-ischemicvalue)Versu

4、sIschemicTime±Preconditioning(PC)+dP/dt(%)VersusIschemicTime±Preconditioning(CPC)EDP(mmHg)VersusIschemicTime±Preconditioning(CPC)BIOCHEMISTRYBIOCHEMISTRYBiochemicalparametersofthehearttissue:asimilarprotectionwasobservedforATP,energycharge,ascorbateandotherparameters.inthecoronaryflow:leakageint

5、otheCFofcellularmetabolites:HPLCAnalysisoftheFirst10-CFFsFollowing35’GlobalIschemiaPC010203040506070Control:ischemiaof35’-noPCPreconditioningfollowedby35’ischemiaSASPUAInoAACurrentlyProposedMechanismsofProtectionbyPCThedetailedunderstandingofthemechanismofPCisstillunderinvestigation.Severalpos

6、sibilitieshavebeensuggestedincluding:adenosineactivation;preservationofhigh-energyphosphates;washoutofmetabolites;roleofCa++-channels;increaseinantioxidantsactivity;synthesisofheat-shockproteins,G-proteins;nitricoxideproduction;roleofK+-channels;roleofPKCWEHAVEBEENSTUDYINGTHEROLESOFIRON,COPPERAN

7、DFREERADICALSINISCHEMIAANDOBTAINEDINDICATIONSFORTHEIRINVOLVEMENTINCARDIACPCROS-ReactiveOxygenSpecies-inreperfusioninjuryTheformationofROSfromrelativelylessreactivespeciesismediatedbyredox-activemetalions.Circumstantialeviden