Decreased circulating thrombomodulin is improved by tadalafil therapy in hypoxemic patients with advanced pulmonary arterial hypertension
Abstract
INTRODUCTION: Advanced pulmonary arterial hypertension (PAH) in patients with congenital cardiac communications and right-to-left shunting (Eisenmenger syndrome - PAH-ES) is associated with hypoxemia and decreased circulating levels of thrombomodulin (TM), probably reflecting decreased endothelial TM production. The combination of these two factors has been shown to induce fibrin deposition, with increased risk of thrombosis, a well known complication in this syndrome.
PATIENTS AND METHODS: We tested the hypothesis that vasodilator therapy with the phosphodiesterase-5 inhibitor tadalafil, an approved drug for management of PAH could improve endothelial dysfunction markers, in particular plasma TM, in addition to improving the physical capacity (expected effect of pulmonary vasodilatation) in PAH-ES patients. This was a prospective observational study of treatment-naïve patients subjected to specific PAH therapy. Fifteen patients aged 12 to 51years (median 30years) were treated for 6months with a single daily dose of 40mg oral tadalafil. The physical capacity (distance walked during the 6-min walk test - 6MWD), systemic oxygen saturation and laboratory parameters were measured at baseline, and 90days and 180days of treatment.
RESULTS: Plasma TM, which was decreased at baseline compared to controls (p<0.001) increased at 90 and 180days (p=0.003), and this was directly related (r=0.57, p=0.026) to improvement of oxygen saturation (p=0.008). Heightened baseline tissue-type…
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