Latest news on Pulmonary arterial hypertension

Regardless of underlying cause or associations, several inter related mechanisms play a role in the development and maintenance of PAH. These mechanisms are mediated by one or more molecular and cellular processes, including reduced prostacyclin availability due to diminished endothelial cell prostacyclin synthase activity, elevated endothelin levels resulting from enhanced production and reduced pulmonary clearance, decreased nitric oxide synthase expression, elevated plasma and low platelet 5-HTT levels, down regulation of voltage dependent potassium Kv1.5 channels of pulmonary vascular smooth muscle cells, activity of autoantibodies and pro-inflammatory cytokines and prothrombotic states arising from endothelial, coagulation and fibrinolytic cascade and platelet dysfunction.

The result of these abnormalities gives rise to a predisposition of vasoconstriction

over vasodilation of the pulmonary vasculature, to excess cellular proliferation which

outpaces apoptosis and to a thrombotic diathesis. The occurrence of dynamic increase 

of pulmonary vascular resistance appears to be an early substrate of PAH, with intimal 

hyperplasia due to endothelial cell proliferation, medial thickening due to vascular 

smooth muscle cell proliferation, development of plexiform lesions caused by disordered 

endothelial proliferation, and thrombosis becoming more prominent during the clinically 

apparent stages of the disease.

Appreciation of the underlying mechanisms of disease points to the means by which

pharmacologic treatment can be utilized to counteract their consequences. The

management of patients with PAH consists of first identifying the presence of PH and

then defining the precise clinical context of the abnormal hemodynamic state, including 

the severity of problem, the associated or casual conditions, the functional implications, 

and the prognosis. This information is required in order to design the optimal therapeutic 

approach.

The basic diagnostic strategy, therefore, is to screen for PH in symptomatic or high

risk patients, then to systematically examine potential underlying conditions with

appropriate tests, delineate predictive factors, perform functional assessment, and to

confirm the hemodynamic profile by invasive testing. There are symptoms which

require consideration of PH, findings on physical examination which are important for

detecting PH and guiding further evaluation. Although no current treatment of PAH can 

be considered curative, realistic goals of treatment are to reduce pulmonary vascular 

resistance and pressure, diminish symptoms and promote activity tolerance and prolong 

longevity.