肺动脉高压的治疗

关于肺动脉高压治疗新进展

肺动脉高压的治疗 Pulmonary Hypertension (PHT)

蒋雷服

关于肺动脉高压治疗新进展

Targets for Therapies in PAH

Humbert, M. et al. N Engl J Med 2004;351:1425-1436

关于肺动脉高压治疗新进展

前列环素 (Prostacyclin)– Prostacyclin( Prostagladin I2, PGI2) produce in vascular endothelium and smooth muscle cell (SMC) induce potent vasodilation, inhibit platelet aggregation, and antiproliferation maintain the low pulmonary vascular tone, prevent vascular remodeling PPH patients prostacyclin level is decreased– Christman. N Engl J Med.1992;327:70

关于肺动脉高压治疗新进展

前列环素--持续静脉内滴注 ( 依前列醇 Epoprostenol, Flolan ) 原发性肺动脉高压(PPH): Barst.(North American PPH Study Group) 12-wk prospective, randomized, multicenter trial in 81 severe PPH patients (NYHA class III or IV) improved exercise capacity(6 m walk ), indexes of the quality of life, and survival; mPAP , PVR ,– N Engl J Med.1996 ;334:296

关于肺动脉高压治疗新进展

依前列醇- 持续静脉内滴注 ( Epoprostenol) 硬皮病引起的肺动脉高压– Badesch (PHT in Scleroderma Spectrum of Disease Study Group) – randomized, controlled trial, 17 centers, 111 patients – improved exercise capacity(6 m walk) , NYHA class and dyspea scores. – mPAP , PVR Ann Intern Med.2000;132:425

关于肺动脉高压治疗新进展

曲前列环素-- 持续皮下输注 (Treprostinil (Remodulin ), UT-15 )– chemical stable, longer half-life – 12 week,double-blind, randomized, placebocontrolled,and multicenter trial in 470 PAH patients Improved exercise capacity,indices of dyspnea, signs and symptoms in PAH Simonneau (European,USA). Am J Respir Crit Care Med.2002;165:800

– 结缔组织疾病伴PAH Ouidz 2004

– 静脉应用转换至皮下 Vachiery 2002

关于肺动脉高压治疗新进展

贝前列环素--口服 ( Beraprost,Dorner )– Arterial Pulmonary Hypertension and Beraprost European Trial (ALPHABET) Study Group a randomized, double-blind, placebo-controlled trial. 130 PAH patients improve exercise capacity and symptoms– Galie.2002 – Barst 2003

–与西地那非合并应用 Ikeda 2005

– 疗效差于 epoprotenol Berman 2004

关于肺动脉高压治疗新进展

伊洛前列素(万他维)--吸入 Iloprost (Ventavis )– The Aerosolized Iloprost Randomized Study Group severe pulmonary hypertension large (203 ), placebo-controlled trial walk distance, hemodynamic, NYHA class, quality of life– Olschewski. 2002

– HIV-related PAH Ghofrani 2004

– 妊娠伴PAH Elliot 2005

关于肺动脉高压治疗新进展

内皮素受体拮抗剂– Endothelin-1 potent endogenous vasoconstrictor, smooth muscle mitogen overexpressed in plasma and lung tissue of patients with PPH and scleroderma

– mediated by two receptors, ETA and ETB Activation of both ETA and ETB on SMC leads to vasoconstriction Activation of ETB on endothelial cells leads to vasodilation– Fagan 2001

关于肺动脉高压治疗新进展

波生坦，Bosentan (Tracleer ) oral antagonist of both endothelin receptors– Pulmonary Arterial Hypertension (PAH) Improves exercise capacity, Borg dysp

nea, and WHO class , Reduced clinical worsening– – – – Channick RN. Lancet. 2001;358:1119 Rubin LJ. N Engl J Med 2002;346:896 Sitbon O. 2003 McLaughlin 2005

– Systemic Sclerosis associated with PAH Humbert M. . 2003

– 门 脉 高 压 患 者 合 并 PAH Hoeper 2005

关于肺动脉高压治疗新进展

Selective ETAreceptor Antagonists– 西地生坦 (Sitaxsentan) Barst RJ. Chest. 2002;121:1860 Barst RJ.. 2004 Langleben 2004

– 安贝生坦(Ambrisentan) Galie 2005

关于肺动脉高压治疗新进展

治疗:一氧化氮(NO) 一氧化氮(nitric oxide, NO) synthesized from L- arginine and O2 by NO synthase(NOS), activate sGC, increase cGMP maintain normal low pulmonary vascular tone, oppose increases in tone caused by hypoxia or other vasoconstrictors. level of exhaled NO is reduced in patients with PPH– Cremona, QJM 1994; 87: 547

关于肺动脉高压治疗新进展

一氧化氮吸入- 急性血管舒张试验:- Sitbon.Am J Respir Crit Care Med. 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–Cardiac Output (CO) ,PAP ,PVR . – Hoeper. J Am Coll Cardiol.2000;35:176

“桥” 肺移植–Snell. Am J Respir Crit Care Med. 1995;151:1263

Ambulatory delivery system–Channick. Am J Respir Crit Care Med. 1994;1482

关于肺动脉高压治疗新进展

一氧化氮吸入(2)–慢性阻塞性肺疾病(COPD): 单纯吸入NO : PAP ,PVR , SAP –Adnot. Am Rev Respir Dis 1993;148:310 –Moinard. Am J Respir Crit Care Med 1994;149:1482 –Vizza. Crit Care 2001;5:355 –Ashutosh. Thorax 2000;55:109 –Kanniess.Respir Med 2001;95:927

GOLD (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 ,PVR –Germann Chest. 1998;114:29

PaO2 ? , PaCO2 ?, CO ?

关于肺动脉高压治疗新进展

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 NO cGMP , PDE cGMP 原发性肺动脉高压– – – – – Wilkens. Circulation.2001;104:1218 Abrams.Heart.2000;84:E4 Jackdson. Int J Clin Pract.2002;56:397 Michelakis. Circulation. 2002;105:2398 Ghofrani. Ann Intern Med. 2002;136:515

关于肺动脉高压治疗新进展

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