肺动脉高压的治疗PPT资料.ppt

肺动脉高压的治疗PPT资料.ppt

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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PAHHoeper2005SelectiveETAreceptorAntagonists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;

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:

5155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:

1509PAH,ClassIII/IVConventionaltherapy（C）（oralanticoagu