从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件

从兴奋收缩耦联机制看心力衰竭正性肌力药物发展田野教授哈医大二院心内科从兴奋收缩耦联机制看心力衰竭1提要目兴奋收缩耦联机制目正性肌力药的循证研究洋地黄制剂β-肾上腺素能受体激动剂磷酸二酯酶抑制剂钙增敏剂目新型正性肌力药的探索亚硝酰氢提要2兴奋-收缩耦联机制兴奋-收缩耦联机制3106/201918:02:1615106/201918:02:4Excitation-contractioncouplingElExcitation-contraction(C)couplingisatermcoinedin1952todescribethephysiologicalprocessofconvertinganelectricalstimulustomechanicalresponse.SandowA(1952)."Excitation-contractioncouplinginmuscularresponse.'YaleBiolMed25(3):176-201.PMID130159500Excitation-contractioncouplin5Cardiacexcitation-contractioncouplingaCardiacexcitation-contractioncouplingistheprocessfromelectricalexcitationofthemyocytetocontractionoftheheart(whichpropelsbloodout).Theubiquitoussecondmessengerca2+isessentialincardiacelectricalactivityandisthedirectactivatorofthemyofilaments,whichcausecontraction.Bers,D.M.Excitation-ContractionCouplingandCardiacContractileForceedn2(KluwerAcademic,Dordrecht,Netherlands,2019)Cardiacexcitation-contraction6CardiactissueACardiactissue(Guinea-pigventricularcell)Cardiactissue7CardiaccellsPathofAPSurfaceofmusclefibera+中MyofibrilsSarcoplasmicreticulumTtubuleTtubuleMacromereCardiaccells8TheactionpotentialmovesthroughsarcolemmaActionpotentialTtubeSarcomereinmyofibril(locatedinsarcoplasm)Theactionpotentialmoves9Ca2+-inducedCa2+-releaseSarcolemmaa*/Ca+ExchangerL-TypeCa2+ChannelCa2州SERCASRCa2+-inducedCa2+-release10从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件11从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件12从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件13从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件14从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件15从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件16从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件17从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件18从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件19从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件20从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件21从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件22从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件23从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件24从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件25从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件26从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件27从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件28从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件29从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件30从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件31从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件32从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件33从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件34从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件35从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件36从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件37从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件38从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件39从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件40从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件41从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件42从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件43从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件44从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件45从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件46从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件47从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件48从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件49从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件50从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件51从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件52从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件53从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件54从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件55从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件56从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件57从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件58从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件59从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件60从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件61从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件62从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件63从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件64从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件65从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件66从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件67从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件68从兴奋收缩耦联机制看心力衰竭正性肌力药物发展课件69从