肺动脉高压的发病机制和药物治疗进展
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摘要
肺动脉高压(PAH)是一种少见的,预后不良的进展性疾病,其主要特征为肺血管阻力增加和肺血管压力持续升高,最终结局是右心衰竭和过早死亡[1]。PAH的病因不尽相同,所以针对不同的临床症状和发病原因,PAH的治疗药物和治疗方法也较多。本文就PAH的发病机制以及临床中常见的治疗药物进行综述。
Pulmonary arterial hypertension(PAH)is a rare,prognostic,progressive disorder,characterized by increased pulmonary vascular resistance and sustained elevation of pulmonary vascular pressure,causing right ventricular failure which leads to eventual death if untreated.The causes of PAH are not the same,so there are diverse treatments and medications for different clinical symptoms and causes of PAH.This article reviews the pathophysiology of pulmonary hypertension and the common drugs for the treatment of pulmonary hypertension in the clinic.
Pulmonary arterial hypertension(PAH)is a rare,prognostic,progressive disorder,characterized by increased pulmonary vascular resistance and sustained elevation of pulmonary vascular pressure,causing right ventricular failure which leads to eventual death if untreated.The causes of PAH are not the same,so there are diverse treatments and medications for different clinical symptoms and causes of PAH.This article reviews the pathophysiology of pulmonary hypertension and the common drugs for the treatment of pulmonary hypertension in the clinic.
引文
[1]Pulmonary hypertension 2015:current definitions,terminology,and novel treatment options[J].Clin Res Cardiol,2015,104(3):197-207.
[2]Robinson JC,Pugliese SC,Fox DL.Anticoagulation in pulmonary arterial hypertension[J].Curr Hypert Rep,2016,18(6):47-47.
[3]Lan NSH,Massam BD,Kulkarni SS.Pulmonary arterial hypertension:pathophysiology and treatment[J].Diseases,2018,6(2):E38.
[4]鄢高亮,盛祖龙,周千星,等.整合素连接激酶在低氧诱导肺动脉高压发病机制中的作用[J].临床心血管病杂志,2017,33(2):178-182.
[5]Konduri GG,Afolayan AJ,Eis A,et al.Interaction of endothelial nitric oxide synthase with mitochondria regulates oxidative stress and function in fetal pulmonary artery endothelial cells[J].Am J Physiol,2015,309(9):L1009-1017.
[6]Mubarak KK.A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension[J].Respir Med,2010,104(1):9-21.
[7]Lajoie AC,Lauzière G,Lega JC,et al.Combination therapy versus monotherapy for pulmonary arterial hypertension:a meta-analysis[J].Lancet Respir Med,2016,4(4):291-305.
[8]Tabima DM,Frizzell S.Reactive oxygen and nitrogen species in pulmonary hypertension[J].Free Radic Biol Med,2012,52(9):1970-1986.
[9]Marra AM,Bossone E,Salzano A,et al.Biomarkers in pulmonary hypertension[J].Heart Fail Clin,2018,14(3):393-402.
[10]王俊贤,马倍,刘珍君,等.过表达ACE2基因的骨髓间充质干细胞对肺动脉高压大鼠的干预作用[J].临床心血管病杂志,2018,34(4):396-402.
[11]Sitbon O,Humbert M,Ja6s X,et al.Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension[J].Circulation,2005,111(23):3105-3111.
[12]GalièN,Humbert M,Vachiery JL,et al.2015ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension[J].Eur Respir J,2015,46(4):903-975.
[13]Pepke-Zaba J,Higenbottam TW,Dinh-Xuan AT,et al.Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension[J].Lancet,1991,338(8776):1173-1174.
[14]Cueto E,López-Herce J,Sánchez A.Life-threatening effects of discontinuing inhaled nitric oxide in children[J].Acta Paediatrica,1997,86(12):1337-1339.
[15]杨京华,朱晨曦,王增智,等.贝前列素钠联合西地那非治疗肺动脉高压的临床观察[J].心肺血管病志,2014,33(6):816-819.
[16]于亦华.西地那非在高原地区先天性心脏病合并肺动脉高压中的应用[J].临床心血管病杂志,2010,26(10):787-788.
[17]GalièN,Ghofrani HA,Torbicki A,et al.Sildenafil citrate therapy for pulmonary arterial hypertension[J].New Engl J Med,2005,353(20):2148-2157.
[18]GalièN,Brundage BH,Ghofrani HA,et al.Tadalafil therapy for pulmonary arterialhypertension[J].Circulation,2009,119(22):2894-2903.
[19]郑泽琪,李宾公,王梦洪,等.阿托伐他汀联合西地那非治疗肺动脉高压的临床研究[J].临床心血管病杂志,2011,27(5):352-354.
[20]Rai N,Veeroju S,Schymura Y,et al.Effect of riociguat and sildenafil on right heart remodeling and function in pressure overload induced model of pulmonary arterial banding[J].Biomed Res Int,2018,2018:3293584.
[21]Badesch DB,Tapson VF,McGoon MD,et al.Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease A randomized,controlled trial[J].Ann Inter Med,2000,132(6):425-434.
[22]Tapson VF,Jing ZC,Xu KF,et al.Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5inhibitor therapy(the FREEDOM-C2 study):a randomized controlled trial[J].Chest,2013,144(3):952-958.
[23]Jing ZC,Parikh K,Pulido T,et al.Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension:a randomized,controlled trial[J].Circulation,2013,127(5):624-633.
[24]Simonneau G,Barst RJ,Galie N,et al.Continuous subcutaneous infusion of treprostinil,aprostacyclin analogue,in patients with pulmonary arterial hypertension:a double-blind,randomized,placebo-controlled trial[J].Am J Respir Crit Care Med,2002,165(6):800-804.
[25]Olschewski H,Hoeper MM,Behr J,et al.Long-term therapy with inhaled iloprost in patients with pulmonary hypertension[J].Respir Med,2010,104(5):731-740.
[26]Olschewski H,Simonneau G,GalièN,et al.Inhaled iloprost for severe pulmonary hypertension[J].New Engl J Med,2002,347(5):322-329.
[27]Rubin LJ,Badesch DB,Barst RJ,et al.Bosentan therapy for pulmonary arterial hypertension[J].New Engl JMed,2002,346(12):896-903.
[28]Humbert M,Segal ES,Kiely DG,et al.Results of European post-marketing surveillance of bosentan in pulmonary hypertension[J].Eur Respir J,2007,30(2):338-344.
[29]GalièN,Palazzini M,Leci E.Current therapeutic approaches to pulmonary arterial hypertension[J].Rev Esp Cardiol,2010,63(6):708-724.
[30]GalièN,Olschewski H,Oudiz RJ,et al.Ambrisentan for the treatment of pulmonary arterial hypertension:results of the ambrisentan in pulmonary arterial hypertension,randomized,double-blind,placebo-controlled,multicenter,efficacy(ARIES)study 1and 2[J].Circulation,2008,117(23):3010-3019.
[31]McGoon MD,Frost AE,Oudiz RJ,et al.Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities[J].Chest,2009,135(1):122-129.
[32]Pulido T,Adzerikho I,Channick RN,et al.Macitentan and morbidity and mortality in pulmonary arterial hypertension[J].New Engl J Med,2013,369(9):809-818.
[33]张卫芳,葛晓月,祝田田,等.缺氧相关性肺动脉高压新靶标:LOX-1[J].临床心血管病杂志,2018,34(5):524-527.
[2]Robinson JC,Pugliese SC,Fox DL.Anticoagulation in pulmonary arterial hypertension[J].Curr Hypert Rep,2016,18(6):47-47.
[3]Lan NSH,Massam BD,Kulkarni SS.Pulmonary arterial hypertension:pathophysiology and treatment[J].Diseases,2018,6(2):E38.
[4]鄢高亮,盛祖龙,周千星,等.整合素连接激酶在低氧诱导肺动脉高压发病机制中的作用[J].临床心血管病杂志,2017,33(2):178-182.
[5]Konduri GG,Afolayan AJ,Eis A,et al.Interaction of endothelial nitric oxide synthase with mitochondria regulates oxidative stress and function in fetal pulmonary artery endothelial cells[J].Am J Physiol,2015,309(9):L1009-1017.
[6]Mubarak KK.A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension[J].Respir Med,2010,104(1):9-21.
[7]Lajoie AC,Lauzière G,Lega JC,et al.Combination therapy versus monotherapy for pulmonary arterial hypertension:a meta-analysis[J].Lancet Respir Med,2016,4(4):291-305.
[8]Tabima DM,Frizzell S.Reactive oxygen and nitrogen species in pulmonary hypertension[J].Free Radic Biol Med,2012,52(9):1970-1986.
[9]Marra AM,Bossone E,Salzano A,et al.Biomarkers in pulmonary hypertension[J].Heart Fail Clin,2018,14(3):393-402.
[10]王俊贤,马倍,刘珍君,等.过表达ACE2基因的骨髓间充质干细胞对肺动脉高压大鼠的干预作用[J].临床心血管病杂志,2018,34(4):396-402.
[11]Sitbon O,Humbert M,Ja6s X,et al.Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension[J].Circulation,2005,111(23):3105-3111.
[12]GalièN,Humbert M,Vachiery JL,et al.2015ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension[J].Eur Respir J,2015,46(4):903-975.
[13]Pepke-Zaba J,Higenbottam TW,Dinh-Xuan AT,et al.Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension[J].Lancet,1991,338(8776):1173-1174.
[14]Cueto E,López-Herce J,Sánchez A.Life-threatening effects of discontinuing inhaled nitric oxide in children[J].Acta Paediatrica,1997,86(12):1337-1339.
[15]杨京华,朱晨曦,王增智,等.贝前列素钠联合西地那非治疗肺动脉高压的临床观察[J].心肺血管病志,2014,33(6):816-819.
[16]于亦华.西地那非在高原地区先天性心脏病合并肺动脉高压中的应用[J].临床心血管病杂志,2010,26(10):787-788.
[17]GalièN,Ghofrani HA,Torbicki A,et al.Sildenafil citrate therapy for pulmonary arterial hypertension[J].New Engl J Med,2005,353(20):2148-2157.
[18]GalièN,Brundage BH,Ghofrani HA,et al.Tadalafil therapy for pulmonary arterialhypertension[J].Circulation,2009,119(22):2894-2903.
[19]郑泽琪,李宾公,王梦洪,等.阿托伐他汀联合西地那非治疗肺动脉高压的临床研究[J].临床心血管病杂志,2011,27(5):352-354.
[20]Rai N,Veeroju S,Schymura Y,et al.Effect of riociguat and sildenafil on right heart remodeling and function in pressure overload induced model of pulmonary arterial banding[J].Biomed Res Int,2018,2018:3293584.
[21]Badesch DB,Tapson VF,McGoon MD,et al.Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease A randomized,controlled trial[J].Ann Inter Med,2000,132(6):425-434.
[22]Tapson VF,Jing ZC,Xu KF,et al.Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5inhibitor therapy(the FREEDOM-C2 study):a randomized controlled trial[J].Chest,2013,144(3):952-958.
[23]Jing ZC,Parikh K,Pulido T,et al.Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension:a randomized,controlled trial[J].Circulation,2013,127(5):624-633.
[24]Simonneau G,Barst RJ,Galie N,et al.Continuous subcutaneous infusion of treprostinil,aprostacyclin analogue,in patients with pulmonary arterial hypertension:a double-blind,randomized,placebo-controlled trial[J].Am J Respir Crit Care Med,2002,165(6):800-804.
[25]Olschewski H,Hoeper MM,Behr J,et al.Long-term therapy with inhaled iloprost in patients with pulmonary hypertension[J].Respir Med,2010,104(5):731-740.
[26]Olschewski H,Simonneau G,GalièN,et al.Inhaled iloprost for severe pulmonary hypertension[J].New Engl J Med,2002,347(5):322-329.
[27]Rubin LJ,Badesch DB,Barst RJ,et al.Bosentan therapy for pulmonary arterial hypertension[J].New Engl JMed,2002,346(12):896-903.
[28]Humbert M,Segal ES,Kiely DG,et al.Results of European post-marketing surveillance of bosentan in pulmonary hypertension[J].Eur Respir J,2007,30(2):338-344.
[29]GalièN,Palazzini M,Leci E.Current therapeutic approaches to pulmonary arterial hypertension[J].Rev Esp Cardiol,2010,63(6):708-724.
[30]GalièN,Olschewski H,Oudiz RJ,et al.Ambrisentan for the treatment of pulmonary arterial hypertension:results of the ambrisentan in pulmonary arterial hypertension,randomized,double-blind,placebo-controlled,multicenter,efficacy(ARIES)study 1and 2[J].Circulation,2008,117(23):3010-3019.
[31]McGoon MD,Frost AE,Oudiz RJ,et al.Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities[J].Chest,2009,135(1):122-129.
[32]Pulido T,Adzerikho I,Channick RN,et al.Macitentan and morbidity and mortality in pulmonary arterial hypertension[J].New Engl J Med,2013,369(9):809-818.
[33]张卫芳,葛晓月,祝田田,等.缺氧相关性肺动脉高压新靶标:LOX-1[J].临床心血管病杂志,2018,34(5):524-527.