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外文资料--Steeper Action Potential Duration Restitution Slope.PDF

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外文资料--Steeper Action Potential Duration Restitution Slope.PDF

STEEPERACTIONPOTENTIALDURATIONRESTITUTIONSLOPEINCREASESRISKOFVENTRICULARFIBRILLATIONASIMULATIONSTUDYYIZHENG1,2,DAMINGWEI2,,ANDZUXIANGFANG11DEPTOFELECTRONICENGINEERING,FUDANUNIVERSITY,SHANGHAI,PEOPLE’SREPUBLICOFCHINA2GRADUATESCHOOLOFCOMPUTERSCIENCEANDENGINEERING,UNIVERSITYOFAIZU,AIZUWAKAMATSU,FUKUSHIMA9658580,JAPANCORRESPONDINGAUTHORDMWEIUAIZUACJPABSTRACTACTIONPOTENTIALDURATIONRESTITUTIONAPDRISTHOUGHTTOBERELEVANTTOTHESTABILITYOFCARDIACELECTROPHYSIOLOGYVENTRICULARFIBRILLATIONVFWASSIMULATEDUSINGTHEWEIHARUMIMODELBYTAKINGINTOACCOUNTPIECEWISELINEARACTIONPOTENTIALDURATIONRESTITUTIONBASEDONCLINICALFINDINGSWEFOUND,INTHESIMULATION,THATHEARTMODELWITHSTEEPERSLOPEOFAPDRREQUIREDLESSECTOPICSTIMULITOTRIGGERVFTHISRESULTSUGGESTEDTHATTHEAPDRMAYAFFECTCARDIACVULNERABILITYTOVFKEYWORDSACTIONPOTENTIALDURATION;RESTITUTION;VENTRICULARFIBRILLATION;SIMULATIONIINTRODUCTIONARRHYTHMIASCAUSEDBYCARDIOVASCULARDISEASESAREPREVALENTHEALTHPROBLEMSINTHEINDUSTRIALIZEDCOUNTRIES1AMONGWHICHTHEVENTRICULARFIBRILLATIONVFISCONSIDEREDASTHEMOSTMALIGNANTARRHYTHMIANOTORIOUSASTHEMOSTCOMMONMECHANISMOFSUDDENCARDIACDEATHSCD24THATANNUALLYACCOUNTSFOROVER30,000DEATHSINTHEUNITEDSTATESALONE5MACWILLIAMCHARACTERIZEDVFASTHEVENTRICULARMUSCLEISTHROWNINTOASTATEOFIRREGULARARRHYTHMICCONTRACTION’’;CONSEQUENTLYMAKETHEHEARTLOSEITSABILITYOFPUMPINGBLOOD6DESPITEDECADESOFENDEAVORFROMACADEMICIANSANDSCHOLARS,THEMECHANISMUNDERLYINGVFREMAINSCONTROVERSIAL7,8LITERATURESSUGGESTTHATACTIONPOTENTIALDURATIONAPDRESTITUTIONISRELEVANTTOTHESTABILITYOFCARDIACELECTROPHYSIOLOGYANDVULNERABILITYTOVFBOTHINVIVO9,10ANDINVITRO11;THISISFURTHERCONFIRMEDINSIMULATION1214INDUCIBILITYOFREENTRYNASHCOMBINEDCLINICALSTUDYWITHSIMULATIONTOTHEREEMPHASIZESIGNIFICANCEOFAPDRESTITUTION15APDRESTITUTIONSEEFIG1ISREFERREDASFUNCTIONBETWEENAPDANDITSPRECEDINGDIASTOLICINTERVALDI16RESEARCHERSHAVEALSOSHOWNTHEPOSSIBILITYOFELIMINATINGVENTRICULARFIBRILLATIONBYFLATTINGAPDRESTITUTION12,17THATMAYFACILITATETHEINVENTIONOFNOVELANTIARRHYTHMIAPHARMACYTHEWEIHARUMIMODEL18,19,ASTATEOFARTHEART3DMODEL,WITHINTEGRATIONOFAPDRESTITUTIONISUTILIZEDINTHISSTUDYTOINVESTIGATETHEPOSSIBLECORRELATIONOFSLOPEOFAPDRESTITUTIONTOINDUCIBILITYOFVENTRICULARFIBRILLATIONITCONSISTSOFOVER50,000CARDIACCELLSWITHREALISTICHEARTANDTORSOANATOMYASWELLASELECTROPHYSIOLOGICALSETTINGCAPABLEOFSIMULATINGBODYSURFACEPOTENTIALMAPBSPMECGANDDEPICTINGACTIVATIONPROPAGATIONATWHOLEHEARTLEVEL20FIGURE1APDROFENDOCARDIUMDERIVEDFROMTEN’SCELLULARMODEL21THISCURVEISOBTAINEDBYAPPLYINGSTIMULITOTHEMODELCELLUSINGDYNAMICRESTITUTIONPROTOCOL16THESTIMULATIONSTRENGTHISTWICEOFTHEDIASTOLICTHRESHOLDWITHANDURATIONOFONEMILLISECONDWORKFROMPHYSICIANSINDICATESTHATHIGHRISKPATIENTSWITHINDUCIBLEVTORALTERNANTTWAARECONNECTEDWITHSTEEPERSLOPEOFAPDRESTITUTIONOVERTHATOFLOWRISKONES10,THATINSPIRESUSTOTAKEADVANTAGEOFTHEWEIHARUMIMODELTODETERMINEWHETHERSTEEPERSLOPELINKSTOHIGHERVULNERABILITYTOVFIIMETHODSACOMBINATIONOFPIECEWISELINEARAPDRESTITUTIONTHEORIGINALSETTINGOFWEIHARUMIMODELASSUMEDTHATTHEVARIATIONOFACTIONPOTENTIALDURATIONISLINEARWITHTHEINCREMENTDECREMENTOFCOUPLINGINTERVALSOTHATDURINGSIMULATIONTHECELLULARAPDISDYNAMICALLYMODIFIEDBYTHEEQUATION1BELOW19APDAPD1DCCITTT⋅Δ1WHERECITΔISTHEINCREMENTDECREMENTOFCARDIACCELLULARCOUPLINGINTERVALATTIMETRESEARCHERSHAVEFOUNDTHATWHILEPACINGSOMECARDIACCELLSATARELATIVELYLONGINTERVAL,EACHACTIVATEDACTIONPOTENTIALBYCORRESPONDINGSTIMULATIONISIDENTICALCALLED11BEHAVIOR,AFTERTHEPACINGRHYTHMEXCEEDSCERTAINCRITICALRATE,APDBIFURCATIONOCCURSDOUBLEPERIODICALSTIMULIGENERATETHISRESEARCHISSUPPORTEDBYSHANGHAILEADINGACADEMICDISCIPLINE,PROJECTNUMBERB112;ANDTHEGRANTINAIDFORSCIENTIFICRESEARCH,NO21500297,JAPANSOCIETYFORTHEPROMOTIONOFSCIENCEJSPS9781424447138/10/25002010IEEETWODIFFERENTACTIONPOTENTIALSONESHORT,ONELONG22,ANDTHISPHENOMENONISRECOGNIZEDASAPDALTERNANTCONSIDEREDASONEOFTHEPOTENTIALTRIGGERSOFUNIDIRECTIONALBLOCKWHICHMAYCONSEQUENTLYINDUCEREENTRYANDEVENARRHYTHMIA5EXPERTSSUGGESTTHATTHEAPDSHALLBEESTIMATEDBYITSFOLLOWEDDIASTOLICINTERVALWHICHISTHEPERIODBETWEENONSETOFTHESTIMULATIONANDTHETIMEOFAPD9011THEEXPERIMENTALACQUIREDSTANDARDRESTITUTIONCURVESDIVERSUSAPDAREUSUALLYFITTEDWITHTHEMONOEXPONENTIALFUNCTIONS15;WHILEHANETALSUGGESTEDTHATPIECEWISEMONOEXPONENTIALFUNCTIONCOULDREFLECTTHERESTITUTIONPROPERTYMOREFAITHFULLY23NEVERTHELESS,PIECEWISELINEARFUNCTIONISADAPTEDINTHISMODELTODEPICTTHEAPDRESTITUTIONFORTHESAKEOFSPEEDYCOMPUTATIONANDSTILLTHISSIMPLICITYCANHARDLYHAMPERSIMULATIONSFROMDERIVINGSATISFYINGRESULTSTHUSTHEAPDISDETERMINEDBYMIN11MIN12212332MAXMAXMINIMUMDIDIADIBDIDIDIADIBDIDIDIADIBDIDIDIMAXIMUMDIDIAPD⋅⋅⋅⎧⎪⎪⎪⎨⎪⎪⎪⎩2WHEREDIISTHEPRECEDINGDIASTOLICINTERVALITSHOULDBENOTEDTHATDICANBENEGATIVESINCETHEECTOPICSTIMULATIONSMAYFALLINTHEACTIONPOTENTIALWHENTHECELLHASNOTREACHEDITS90REPOLARIZATIONBMODIFICATIONOFABSOLUTEREFRACTORYPERIODSETTINGINWEIHARUMIMODEL,EACHCELLULARABSOLUTEREFRACTORYPERIODARPISDEFINEDBYRESPECTIVECONSTANTPLUSESGRADIENTDIFFERENCEHOWEVER,MICHAELETALPOINTEDOUTTHATUNDERNORMALCONDITIONS,APD90ANDERPWASPROPORTIONALTOTHECYCLELENGTHS24,THUSINTHISSTUDYARPISSETTOBE90OFCORRESPONDINGAPD90THEDEFINITIONOFAPD90ISTHETIMEBETWEENONSETOFSTIMULATIONAND90REPOLARIZATIONOFACTIONPOTENTIAL25CSIMULATIONOFVENTRICULARFIBRILLATIONINDUCINGRESTITUTIONDATAAREFROMAREPORTBYSELVARAJETAL10,ANDTHEYSHOWEDTHATPATIENTSWITHCARDIOMYOPATHYHIGHRISKOFARRHYTHMIAPOSSESSEDSIGNIFICANTLYSTEEPERMEANACTIVATIONRECOVERYINTERVALEQUIVALENTTOAPDRESTITUTIONSLOPESTHANTHATOFLOWRISKONESTHEPARAMETERSOFRESTITUTIONOFPATIENTSARELISTEDRESPECTIVELYINTABLE1THEPARAMETERSOFEACHPATIENTAREDIVIDEDINTOTHREECATALOGUESACCORDINGTOTHEIRLOCATIONSAPEX,MIDDLEANDBASEOFHEART10TWOMODELSUSINGTHESEPARAMETERSFROMRESPECTIVEPATIENTARESTUDIEDVFISINDUCEDBYPACINGWITHATRAINOFPERIODICALECTOPICSTIMULIAPPLIEDONLEFTVENTRICULAREPICARDIUMOFTHEHEARTMODELINDICATEDBYTHEBLACKARROWINFIG226,27THEONSETOFSTIMULATIONSISTIMEDTOFALLINTHEVULNERABLEPERIODINORDERTOFACILITATEINDUCIBILITYOFFIBRILLATIONINDUCINGOFFIBRILLATIONISREGARDEDASSUCCESSFULIFTHEIRREGULARMORPHOLOGICALSIMULATEDECGPERSISTSAFTERTHERETREATOFECTOPICIMPULSESTHEENTIRESIMULATIONLASTSSIXTHOUSANDMILLISECONDSTABLEIPARAMETERSOFRESTITUTIONPATIENTPARAMETERSMILLISECONDLOCATIONMINIMUMDIMINA1B1D1A2B2LOWRISKAPEX260005726040008280MIDDLE25400642542501267BASE255003625547016264HIGHRISKAPEX50185172707025260MIDDLE40207124712016258BASE302031332431002254PATIENTPARAMETERSMILLISECONDALOCATIOND2A3B3DIMAXMAXIMUMLOWRISKAPEX1250290300290MIDDLE125009269300298BASE107008271300295HIGHRISKAPEX4001266300296MIDDLE135003276300285BASE80008264300288ACONTINUEWITHPREVIOUSTABLEFIGURE2ACROSSSECTIONLOCATEDATABOUTONETHIRDFROMTHEAPEXOFTHEHEARTMODELTHEBLACKARROWINDICATEDDOTINTHERIGHTSIDESHOWSTHEPOSITIONOFECTOPICSTIMULATIONFIGURE3LEADIIOFSINUSRHYTHMANDVFLIKERHYTHMINDUCEDBYMINIMUMECTOPICSTIMULIFROMHEARTMODELSUSINGPARAMETERSFROMRESPECTIVEPATIENTSTHEUPPERPANELINDICATESECGSOFMODELOFLOWRISKPATIENT’SHEART,ANDTHELOWERONEINDICATESTHOSEOFMODELOFHIGHRISKONE’STHEOPENARROWSINTHEPICTUREINDICATETHEONSETANDRETREATTIMEOFECTOPICSIMULATIONSINRESPECTIVEMODEL,NOTETHATTHEMODELOFHIGHRISKPATIENTS’MINIMUMREQUIREDECTOPYISSIGNIFICANTLYSHORTTHANTHATOFMODELOFLOWRISKPATIENTS’FIGURE4INSUFFICIENTECTOPICSTIMULILEADINGTOUNSUCCESSFULVENTRICULARFIBRILLATIONINDUCTIONINTHEHEARTMODELOFHIGHRISKPATIENTASSOONASTHEECTOPICSIMULIRETREAT,THESIMULATEDRHYTHMAUTOMATICLYRESTORESNORMALSINUSRHYTHMIIIRESULTFIG3SHOWSTHELEADIIOFSINUSRHYTHMANDVFLIKERHYTHMFROMBOTHMODELSTHEEXTRASTIMULISTARTABOUT470MSAFTERTHEFIRSTSINUSPACINGANDTHECYCLELENGTHISSLIGHTLYABOVE200MSCOMPARABLEWITHTHEABSOLUTEREFRACTORYPERIODARPTHEOPENARROWSINRESPECTIVEDIAGRAMSINDICATETHETIMEOFONSETANDRETREATOFECTOPICSTIMULI,SINUSIMPULSESCONTINUETILLTHEENDOFTHESIMULATIONAPPARENTLYTHESINUSRHYTHMSOFBOTHMODELSAREIDENTICALFORMODELOFHIGHRISKPATIENT,ATLEAST9SUCCESSIVEECTOPICSTIMULIAREREQUIREDTOINDUCEFIBRILLATION;WHILEINCONTRAST,THEMODELOFLOWRISKDEMANDSATLEAST13STIMULIIFTHEECTOPICSTIMULIAREINSUFFICIENT,THEHEARTMODELCANRESTORESINUSRHYTHMITSELFASMANIFESTEDINFIGURE4,SUGGESTINGTHATHEARTMODELWITHLESSSTEEPAPDRESTITUTIONISMOREROBUSTAGAINSTARRHYTHMIATHISISCONSISTENTWITHSIMULATIONSWHICHPROVETHATREENTRYCANBETERMINATEDBYFLATTINGAPDRESTITUTIONCURVE12,17IVCONCULSIONANDDISCUSSIONACONCLUSIONPREVIOUSLYYAMAKIAETALUSEDWEIHARUMITOSTUDYHOWRESTITUTIONCANAFFECTTHEGENERATIONOFARRHYTHMIAANDCAMEUPWITHSIMILARCONCLUSION28INCURRENTSTUDY,MOREREALISTICRESTITUTIONFEATUREISINTEGRATEDANDYIELDSRESULTAGREESWITHTHECLINICALFINDINGSVFISSUCCESSFULLYSIMULATEDWITHTHREEDIMENSIONALHEARTMODELWEFINDTHATHEARTMODELWITHSTEEPERRESTITUTIONISMOREVULNERABLETOECTOPY,THUSSLOPEOFRESTITUTIONMAYPLAYANIMPORTANTROLEINSTUDYINGVFANDSTEEPERSLOPEOFAPDRPERHAPSINCREASESTHEVULNERABILITYOFHEARTTOTHEVFITISQUITELIKELYTHATSTEEPRESTITUTIONINCREASESTHEELECTROPHYSIOLOGICALHETEROGENEITYOFTHEHEARTWHICHISTHOUGHTTOBEESSENTIALSUBSTRATEFORINDUCINGREENTRYANDEVENARRHYTHMIA29ASDESCRIBEDINWEISSETAL’SPAPER5STEEPRESTITUTIONINDUCESAPDALTERNANS,FORMSSPATIALLYDISTRIBUTEDREFRACTORYPERIODDIFFERENCES,ANDAMPLIFIESTHEVARIATIONSOFEXISTEDHETEROGENEITYBDISCUSSIONDURINGVENTRICULARFIBRILLATION,EACHCELL’SDIISVERYSHORTSOTHATTHESLOPEOFRESTITUTIONISSHARP,SINCETHESLOPEOFRESTITUTIONDECLINESASTHEDIINCREASES,NONLINEARDYNAMICCONTROLMETHODCANBEUTILIZEDTOMANIPULATEDISANDMOVEELECTRICALACTIVITYINTOFLATRESTITUTIONREGION,CONSEQUENTLYSTABILIZETHEKINETICSOFELECTRICALACTIVITYSUCHPROTOCOLWASCERTIFIEDWITHFEEDBACKFEATUREANDPROVENFEASIBLE30THESEFINDINGSMAYFACILITATETHEFUTUREELECTRICALTHERAPYAGAINSTARRHYTHMIAANDEVENDRAMATICALLYREDUCETHEENERGYDEMANDEDBYCONVENTIONALDEFIBRILLATIONACKNOWLEDGMENTTHEAUTHORSWOULDLIKETOTHANKDRXINZHU,DRXIAOMEIWUANDDRCUIWEIYANGFORTHEIRVALUABLEASSISTANCETOSIMULATIONSTUDIESREFERENCES1AMAAHAHEARTDISEASEANDSTROKESTATISTICS2006UPDATE2JROBERT,“SUDDENCARDIACDEATHEXPLORINGTHELIMITSOFOURKNOWLEDGE,”JOURNALOFCARDIOVASCULARELECTROPHYSIOLOGYVOL12,ISSUE3,PP3041,20013EDENGELSTEIN,ANDDPZIPES,“SUDDENCARDIACDEATH,”THEHEART,ARTERIESANDVEINS,VOL16,ISSUE9,PP10811112,19984JNWEISS,PSCHEN,ZQU,HSKARAGUEUZIAN,ANDAGARFINKEL,“VENTRICULARFIBRILLATIONHOWDOWESTOPTHEWAVESFROMBREAKING,”CIRCULATIONRESEARCH,VOL87,ISSUE12,PP11031107,20005JNWEISS,AKARMA,YSHIFERAW,PSCHEN,AGARFINKEL,ANDZQU,ETAL,“FROMPULSUSTOPULSELESSTHESAGAOFCARDIACALTERNANS,”CIRCULATIONRESEAR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