scholarly journals Hemodynamic effects of fluoxetine in pulmonary arterial hypertension: an open label pilot study

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402097195
Author(s):  
Adetoun Sodimu ◽  
Sonja Bartolome ◽  
Oluwatosin P. Igenoza ◽  
Kelly M. Chin

In order to evaluate the therapeutic potential of fluoxetine in pulmonary arterial hypertension, 13 patients with pulmonary arterial hypertension underwent catheterization before and after 12 (N = 5) or 24 (N = 8) weeks fluoxetine therapy. No change was seen in the primary endpoint of pulmonary vascular resistance, other hemodynamic values, or any secondary endpoints.

2018 ◽  
Vol 51 (6) ◽  
pp. 1702638 ◽  
Author(s):  
Anna R. Hemnes ◽  
Anandharajan Rathinasabapathy ◽  
Eric A. Austin ◽  
Evan L. Brittain ◽  
Erica J. Carrier ◽  
...  

Pulmonary arterial hypertension (PAH) is a deadly disease with no cure. Alternate conversion of angiotensin II (AngII) to angiotensin-(1–7) (Ang-(1–7)) by angiotensin-converting enzyme 2 (ACE2) resulting in Mas receptor (Mas1) activation improves rodent models of PAH. Effects of recombinant human (rh) ACE2 in human PAH are unknown. Our objective was to determine the effects of rhACE2 in PAH.We defined the molecular effects of Mas1 activation using porcine pulmonary arteries, measured AngII/Ang-(1–7) levels in human PAH and conducted a phase IIa, open-label pilot study of a single infusion of rhACE2 (GSK2586881, 0.2 or 0.4 mg·kg−1 intravenously).Superoxide dismutase 2 (SOD2) and inflammatory gene expression were identified as markers of Mas1 activation. After confirming reduced plasma ACE2 activity in human PAH, five patients were enrolled in the trial. GSK2586881 was well tolerated with significant improvement in cardiac output and pulmonary vascular resistance. GSK2586881 infusion was associated with reduced plasma markers of inflammation within 2–4 h and increased SOD2 plasma protein at 2 weeks.PAH is characterised by reduced ACE2 activity. Augmentation of ACE2 in a pilot study was well tolerated, associated with improved pulmonary haemodynamics and reduced markers of oxidant and inflammatory mediators. Targeting this pathway may be beneficial in human PAH.


2021 ◽  
pp. 204589402199693
Author(s):  
Etienne-Marie Jutant ◽  
David Montani ◽  
Caroline Sattler ◽  
Sven Günther ◽  
Olivier Sitbon ◽  
...  

Introduction. Sleep-related breathing disorders, including sleep apnea and hypoxemia during sleep, are common in pulmonary arterial hypertension (PAH), but the underlying mechanisms remain unknown. Overnight fluid shift from the legs to the upper airway and to the lungs promotes obstructive and central sleep apnea, respectively, in fluid retaining states. The main objective was to evaluate if overnight rostral fluid shift from the legs to the upper part of the body is associated with sleep-related breathing disorders in PAH. Methods. In a prospective study, a group of stable patients with idiopathic, heritable, related to drugs, toxins, or treated congenital heart disease PAH underwent a polysomnography and overnight fluid shift measurement by bioelectrical impedance in the month preceding or following a one-day hospitalization according to regular PAH follow-up schedule with a right heart catheterization. Results. Among 15 patients with PAH (women: 87%; median [25th;75th percentiles] age: 40 [32;61] years; mean pulmonary arterial pressure 56 [46;68] mmHg; pulmonary vascular resistance 8.8 [6.4;10.1] Wood units), 2 patients had sleep apnea and 8 (53%) had hypoxemia during sleep without apnea. The overnight rostral fluid shift was 168 [118;263] mL per leg. Patients with hypoxemia during sleep had a greater fluid shift (221 [141; 361] mL) than those without hypoxemia (118 [44; 178] mL, p = 0.045). Conclusion. This pilot study suggests that hypoxemia during sleep is associated with overnight rostral fluid shift in PAH.


CHEST Journal ◽  
2017 ◽  
Vol 152 (4) ◽  
pp. A738
Author(s):  
Fernando Torres ◽  
Harrison Farber ◽  
Arsen Ristić ◽  
Vallerie McLaughlin ◽  
John Adams ◽  
...  

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