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1、TheEffectofOralAntiplateletAgentsonTissuePlasminogenActivator-mediatedThrombolysisinaRabbitModelofThromboembolicStrokeBednar,MartinM.M.D.,Ph.D.;Quilley,JohnPh.D.;Russell,SheilaR.A.S.;Fuller,SusanP.B.S.;Booth,ChristinaB.A.;Howard,DianthaM.S.;Gross,CordellE.M.D.AuthorInformationDivisionof
2、Neurosurgery(MMB,SRR,SPF,CB,CEG)andDepartmentofBiostatistics(DH),UniversityofVermont,Burlington,Vermont,andDepartmentofPharmacology,NewYorkMedicalCollege,Valhalla,NewYorkReceived,December13,1995.Accepted,February26,1996.Reprintrequests:MartinM.Bednar,M.D.,Ph.D.,UniversityofVermont,Depar
3、tmentofSurgery,GivenE309C,Burlington,Vermont05405.AbstractOBJECTIVE:Thesuccessofthrombolytictherapyinacutestrokereliesontimelyreperfusion.Thecurrentstudyexaminestheefficacyofantiplateletagentsasadjuvantsforthrombolytictherapy.METHODS:Usinganestablishedrabbitmodelofclotembolizationandara
4、ndomizedblindeddesign,rabbits(n=8ineachgroup)wereorallypretreateddailyfor5dayswithadjuvantaspirin(1mg/kgofbodyweightor20mg/kg),ticlopidine(100mg/kg),orvehicle(sodiumcarbonate).Onthe6thday,tissueplasminogenactivator(6.3mg/kgadministeredintravenouslyover2h),wasinitiated1hourafterembolizat
5、ion.RESULTS:Inallgroups,cerebralbloodflow(CBF)wasreducedto<10ml/100g/minimmediatelyafterclotembolization.Aftertheinitiationoftissueplasminogenactivator(t-PA),therewassignificantrestorationofCBFinthecontrol(t-PAonly)andticlopidinegroups(P<0.05)only.RestorationofCBFgenerallycorrelatedwith
6、braininfarctsize(percenthemisphere,mean±standarderrorofthemean),whichwas18.0±7.0inthet-PAonlygroupversus11.0±3.3,26.5±5.8,and21.5±3.4intheticlopidine,low-doseaspirin,andhigh-doseaspiringroups,respectively(ticlopidineversusaspirin,P<0.05).Clotlysiswasidenticalinthecontrolandticlopidinegr
7、oups,with6of8animalsdemonstratingcompleteclotlysis.Aspirinantagonizedclotlysisinadose-relatedmanner,withlow-andhigh-doseaspiringroupsnotingclotlysisinfourofeightandtwoofeightanimals,respectively.CONCLUSIONS:Pretreatmentwithticlopidinesignificantlyreducedbraininfarctsizewhencomp
