Treatment for pulmonary arterial hypertension-associated right ventricular dysfunction.
Treatment for pulmonary arterial hypertension-associated right ventricular dysfunction.
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DOI：
10.1513/annalsats.201312-425fr
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发表时间：
2014-09-01
影响因子：
8.3
通讯作者：
Bogaard, Harm J
中科院分区：
文献类型：
--
作者：
Gomez-Arroyo, Jose;Sandoval, Julio;Bogaard, Harm J
肺动脉高压（PAH）包括以肺血管收缩和肺循环重塑为特征的异质性疾病。虽然多环芳烃是一种肺部疾病，但多环芳烃患者经常死于右心衰。事实上，PAH患者的生存取决于右心室（RV）对肺循环变化的适应性反应。pah特异性药物通过后负荷减少影响右心室功能，也可能通过直接作用于心肌来影响右心室功能。前列环素、5型磷酸二酯酶抑制剂和胍基环化酶刺激剂可通过增加环腺苷和单磷酸鸟苷的可用性直接增强心肌收缩力。虽然这可能最初改善心脏功能，但对心肌耗氧量和功能的长期影响尚不清楚。内皮素受体拮抗剂的心脏作用可能相反，因为内皮素-1已知可抑制心脏收缩。由于PAH越来越被认为是一种肺血管壁细胞准恶性生长的疾病，因此正在开发抑制肥大和血管生成以及促进细胞凋亡的治疗方法。这些治疗的固有危险是对已经缺血、纤维化和功能失调的右心室的进一步妥协。最近，右心脏已被确定为PAH的直接治疗靶点。目前正在研究左心衰治疗的效果，如β -肾上腺素受体阻滞剂、肾素血管紧张素系统抑制剂、运动训练和辅助装置。未来PAH患者的治疗可能包括多方面的方法，旨在同时降低肺循环压力和改善右心适应性。
Pulmonary arterial hypertension (PAH) includes a heterogeneous group of diseases characterized by pulmonary vasoconstriction and remodeling of the lung circulation. Although PAH is a disease of the lungs, patients with PAH frequently die of right heart failure. Indeed, survival of patients with PAH depends on the adaptive response of the right ventricle (RV) to the changes in the lung circulation. PAH-specific drugs affect the function of the RV through afterload reduction and perhaps also through direct effects on the myocardium. Prostacyclins, type 5 phosphodiesterase inhibitors, and guanylyl cyclase stimulators may directly enhance myocardial contractility through increased cyclic adenosine and guanosine monophosphate availability. Although this may initially improve cardiac performance, the long-term effects on myocardial oxygen consumption and function are unclear. Cardiac effects of endothelin receptor antagonists may be opposite, as endothelin-1 is known to suppress cardiac contractility. Because PAH is increasingly considered as a disease with quasimalignant growth of cells in the pulmonary vascular wall, therapies are being developed that inhibit hypertrophy and angiogenesis, and promote apoptosis. The inherent danger of these therapies is a further compromise to the already ischemic, fibrotic, and dysfunctional RV. More recently, the right heart has been identified as a direct treatment target in PAH. The effects of well established therapies for left heart failure, such as beta-adrenergic receptor blockers, inhibitors of the renin-angiotensin system, exercise training, and assist devices, are currently being investigated in PAH. Future treatment of patients with PAH will likely consist of a multifaceted approaches aiming to reduce the pressure in the lung circulation and improving right heart adaptation simultaneously.