Platelet Serotonin Content and Transpulmonary Platelet Serotonin Gradient in Patients with Pulmonary Hypertension

Abstract

Background: The serotonin system has repeatedly been associated with the pathogenesis of pulmonary hypertension (PH). Objective: To comparatively analyze plasmatic and intrathrombocytic serotonin levels in arterial and mixed venous blood of patients with PH and unaffected controls to elucidate pulmonary serotonin metabolisms. Patients and Methods: Catheters were placed in the radial and pulmonary artery in patients with PH (n = 13) for diagnosis and in age-matched controls (n = 6) undergoing percutaneous closure of the patent foramen ovale. Arterial and mixed venous blood samples were immediately centrifuged to obtain plasma and platelets and thereafter frozen at –20°C. After careful thawing, plasmatic and platelet serotonin levels were determined by ELISA. Results: PH was classified as arterial in 4 and chronic thromboembolic in 9 patients with a mean pulmonary artery pressure of 37 (interquartile range: 32–43) mm Hg. Platelet serotonin content was significantly lower in the PH patients than in the controls. The mean transpulmonary gradient (arterial-mixed venous) was negative in the PH group and positive in the controls. An inverse correlation was found between the arterial blood platelet serotonin content and pulmonary hemodynamics. Plasmatic serotonin levels did not differ between the PH and control groups. Conclusion: The lower platelet serotonin concentration in PH patients compared with unaffected controls is an unprecedented finding. The negative transpulmonary platelet serotonin gradient and the strong negative correlation of arterial blood platelet serotonin with pulmonary hemodynamics might indicate increased serotonin uptake in the lungs of PH patients.

Wrist Actigraphy Predicts Outcome in Patients with Pulmonary Hypertension

“…PH was grouped according to hemodynamics in modest [mean pulmonary artery pressure (mPAP) = 26-39 mm Hg], severe (mPAP ≥40) and very severe (mPAP ≥40 with mixed venous oxygen saturation <60%) [18]. Venous N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured [19,20]. Sleep studies were performed as previously described [14].…”

Thrombosis, platelets, microparticles and PAH: more than a clot

“…There is mounting evidence that serotonin is key to the development of PAH, as increases in plasma serotonin caused by the anorexigen, fenfluramine, markedly increased the chances of developing PAH, and in at least one study, increased serotonin transport was causally linked to smooth muscle cell hypertrophy [55,56]. More recently, a small study demonstrated a negative transpulmonary platelet serotonin gradient in PAH patients, while control subjects exhibited a positive gradient [57]. These data are suggestive that the lungs of PAH patients may take up serotonin from platelets or that altered hemodynamics in the lungs of PAH patients cause degranulation and release of serotonin into the blood.…”

Increased platelet, leukocyte and endothelial microparticles predict enhanced coagulation and vascular inflammation in pulmonary hypertension

“…Hence, an altered function of these cells, especially of platelets, plays a pivotal role in the progression of PH [17]. By releasing coagulatory and inflammatory cytokines, activated platelets induce thromboembolic complications, which is a major cause of death in PH patients, but also enforce vasoconstriction and disease progression [18,19]. Accordingly, in the serum of patients with PH inflammatory and platelet activation markers such as sCD40L and sP-selection are elevated underlining our hypothesis of enhanced platelet activation in PH, which is in our study reflected by increased PMP levels [20,21].…”