肺动脉高压的治疗.ppt

肺动脉高压的治疗.ppt

《肺动脉高压的治疗.ppt》由会员分享，可在线阅读，更多相关《肺动脉高压的治疗.ppt（25页珍藏版）》请在冰点文库上搜索。

肺动脉高压的治疗PulmonaryHypertension（PHT）,蒋雷服,Humbert,M.etal.NEnglJMed2004;351:

1425-1436,TargetsforTherapiesinPAH,前列环素（Prostacyclin）,Prostacyclin（ProstagladinI2,PGI2）produceinvascularendotheliumandsmoothmusclecell（SMC）inducepotentvasodilation,inhibitplateletaggregation,andantiproliferationmaintainthelowpulmonaryvasculartone,preventvascularremodelingPPHpatientsprostacyclinlevelisdecreasedChristman.NEnglJMed.1992;327:

70,原发性肺动脉高压（PPH）:

Barst.（NorthAmericanPPHStudyGroup）12-wkprospective,randomized,multicentertrialin81severePPHpatients（NYHAclassIIIorIV）improvedexercisecapacity（6mwalk）,indexesofthequalityoflife,andsurvival;mPAP,PVR,NEnglJMed.1996;334:

296,前列环素-持续静脉内滴注（依前列醇Epoprostenol，Flolan）,依前列醇-持续静脉内滴注（Epoprostenol）,硬皮病引起的肺动脉高压Badesch（PHTinSclerodermaSpectrumofDiseaseStudyGroup）randomized,controlledtrial,17centers,111patientsimprovedexercisecapacity（6mwalk），NYHAclassanddyspeascores.mPAP,PVRAnnInternMed.2000;132:

425,曲前列环素-持续皮下输注（Treprostinil（Remodulin）,UT-15）,chemicalstable,longerhalf-life12week,double-blind,randomized,placebo-controlled,andmulticentertrialin470PAHpatientsImprovedexercisecapacity,indicesofdyspnea,signsandsymptomsinPAHSimonneau（European,USA）.AmJRespirCritCareMed.2002;165:

800结缔组织疾病伴PAHOuidz2004静脉应用转换至皮下Vachiery2002,贝前列环素-口服（Beraprost，Dorner）,ArterialPulmonaryHypertensionandBeraprostEuropeanTrial（ALPHABET）StudyGrouparandomized,double-blind,placebo-controlledtrial.130PAHpatientsimproveexercisecapacityandsymptomsGalie.2002Barst2003与西地那非合并应用Ikeda2005疗效差于epoprotenolBerman2004,伊洛前列素（万他维）-吸入Iloprost（Ventavis）,TheAerosolizedIloprostRandomizedStudyGroupseverepulmonaryhypertensionlarge（203）,placebo-controlledtrialwalkdistance,hemodynamic,NYHAclass,qualityoflifeOlschewski.2002HIV-relatedPAHGhofrani2004妊娠伴PAHElliot2005,内皮素受体拮抗剂,Endothelin-1potentendogenousvasoconstrictor,smoothmusclemitogenoverexpressedinplasmaandlungtissueofpatientswithPPHandsclerodermamediatedbytworeceptors,ETAandETBActivationofbothETAandETBonSMCleadstovasoconstrictionActivationofETBonendothelialcellsleadstovasodilationFagan2001,波生坦，Bosentan（Tracleer）,oralantagonistofbothendothelinreceptorsPulmonaryArterialHypertension（PAH）Improvesexercisecapacity,Borgdyspnea,andWHOclass,ReducedclinicalworseningChannickRN.Lancet.2001;358:

1119RubinLJ.NEnglJMed2002;346:

896SitbonO.2003McLaughlin2005SystemicSclerosisassociatedwithPAHHumbertM.2003门脉高压患者合并PAHHoeper2005,SelectiveETAreceptorAntagonists,西地生坦（Sitaxsentan）BarstRJ.Chest.2002;121:

1860BarstRJ.2004Langleben2004安贝生坦（Ambrisentan）Galie2005,治疗:

一氧化氮（NO）,一氧化氮（nitricoxide,NO）synthesizedfromL-arginineandO2byNOsynthase（NOS）,activatesGC,increasecGMPmaintainnormallowpulmonaryvasculartone,opposeincreasesintonecausedbyhypoxiaorothervasoconstrictors.levelofexhaledNOisreducedinpatientswithPPHCremona,QJM1994;87:

547,一氧化氮吸入,急性血管舒张试验:

Sitbon.AmJRespirCritCareMed.1995;151:

384原发性肺动脉高压:

德国原发性肺动脉高压研究协作组CardiacOutput（CO）,PAP,PVR.Hoeper.JAmCollCardiol.2000;35:

176“桥”肺移植Snell.AmJRespirCritCareMed.1995;151:

1263AmbulatorydeliverysystemChannick.AmJRespirCritCareMed.1994;1482,一氧化氮吸入

（2）,慢性阻塞性肺疾病（COPD）：

单纯吸入NO:

PAP,PVR,SAPAdnot.AmRevRespirDis1993;148:

310Moinard.AmJRespirCritCareMed1994;149:

1482Vizza.CritCare2001;5:

355Ashutosh.Thorax2000;55:

109Kanniess.RespirMed2001;95:

927GOLD（WHO/NHLBI）推荐应用长期氧疗（LTOT）:

增加运动耐量,延长患者寿命吸入NO+LTOT:

mPAP,PVRGermannChest.1998;114:

29PaO2?

PaCO2?

CO?

5型磷酸二酯酶抑制剂,西地那非（伟哥）（Sidenafil，Viagra）:

磷酸二酯酶（PDE）-5抑制剂NOcGMP,PDEcGMP原发性肺动脉高压Wilkens.Circulation.2001;104:

1218Abrams.Heart.2000;84:

E4Jackdson.IntJClinPract.2002;56:

397Michelakis.Circulation.2002;105:

2398Ghofrani.AnnInternMed.2002;136:

515,5型磷酸二酯酶抑制剂,其他5型磷酸二酯酶抑制剂他达那非（Tadalafil），25mg艾地那非（Vardenafil）,20mg,未来展望:

一氧化氮合酶（nitricoxidesynthaseNOS）基因转移,expressionofendothelialNO-synthase（eNOS）isreducedinlungsofpatientswithPHTGiaid,NEnglJMed1995;333:

214adenoviral-mediatedlNOSgenetransfertorateNOStransfer:

increaseeNOSexpression,reduceacutehypoxicpulmonaryvasoconstriction（HPV）invivoJanssensJClinInvest.1996;98:

317iNOStransfer:

increaseexhaledNOlevel,reducechronichypoxicpulmonaryhypertensionandpulmonaryvascularremodelinginvivoBudts.Circulation.2000;102:

2880eNOSandiNOStransfer:

decreasetheefficacyofvasoconstrictors,increasetheefficacyofendothelium-dependentvasodilatorinisolatedpulmonaryarteriesJiang.AmJRespirCritCareMed.2000;161:

A461,前列环素合酶（prostacyclinsynthasePGIS）基因转移,prostacyclinsynthase（PGIS）locatedintheendotheliumandSMCofarteiries,epithelialdecreasedPGISexpressioninvesselsofPHTpatientssTuder.AmJRespirCritCareMed.1999;159:

1925PGIStransgenicmiceincreasedPGI2levellowerRVSP,novesselwallhypertrophytochronichypoxiaGeraci.JClinInvest.1999;103:

1509,PAH,ClassIII/IV,Conventionaltherapy（C）（oralanticoagulantsdiureticsO2）,ClassIV,Epoprostenol（A）Bosentan（A）Treprostinil（B）,EndothelinRAntagonistsBosentan（A）orProstanoidAnaloguesIloprostinh（B）,Treprostinil（B）,Beraprost（B）,orEpoprostenol（A）,ClassIII,OralCCBs（C）,ContinueCCB（10%）,SustainedResponse,Yes,No,AtrialSeptostomy（C）and/orTransplant（C）,Yes,No,PDE5inhibitorsSildenafil（C）,Noimprovementordeterioration:

CombinationTherapy?

一般治疗,抗凝治疗：

华法林diureticsoxygendigitatisanddobutamine钙通道阻滞剂（calcium-channelblockers）如硝苯地平、氨氯地平等仅10%的PAH患者有效只有急性血管扩张试验阳性患者才能应用,CategoriesofPHandspecificmanagement,PAHSporadicFamilialRelatedAssociatedwithPVOD/PCH*,PvenoushypertensionLeft-sideheartdiseaseLeft-sidevalvulardisease,PHassociatedwithlungdiseaseand/orhypoxemia,PHduetoCTEProximalobstructionDistalobstruction,Miscellaneous,Prostanoids,ERA,PDE5inhibitors?

*Withgreatcautioninthisgroup,ACEinhibitors,BB,others,LTOT,ThromboendarterectomySimilartoPAH?

Norecommendations,Interventionalprocedures,球囊房间隔造口术（Atrialseptostomy）使高压的右心房血液分流入左心房，改善右心功能药物治疗无效的特发性肺动脉高压肺移植（Lungtransplantation）特发性肺动脉高压静脉应用依前列醇治疗无效6MWT350m心功能NYHAIII或IV级,主要参考文献,Tapsonetal.SafetyandefficacyofIVtreprostinilforpulmonaryarterialhypertension.Chest,2006,129:

683-688陆慰萱，王辰主编.肺循环病学.北京，人民卫生出版社，2007Barstetal.Treatmentofpulmonaryarterialhypertensionwiththeselectiveendothelin-Areceptorantagonistsitaxsentain.JAmCollCardiol.2006,47:

2049-2056,主要参考文献,蒋雷服，等.前列环素治疗肺动脉高压的临床应用进展.国际呼吸杂志，2007；27:

1272-1275Singh,etal.Arandomized,placebo-controlled,double-blind,crossoverstudytoevaluatetheefficacyoforalsildenafiltherapyinseverepulmonaryarteryhypertension.AmHeartJ,2006,151:

851.855蒋雷服,等.内皮素受体拮抗剂治疗肺动脉高压的临床应用.国际药学研究杂志，2007,34:

263-266,Thankyouforyourattention！