• Jose Gomez-Arroyo, Julio Sandoval, Marc A Simon, Erick Dominguez-Cano, Norbert F Voelkel, and Harm J Bogaard.
• 1 Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
• Ann Am Thorac Soc. 2014 Sep 1; 11 (7): 1101-15.

AbstractPulmonary 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 β-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.

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