Document Detail


Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema.
MedLine Citation:
PMID:  19520908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Whether pulmonary hypertension at high altitude limits exercise capacity remains uncertain. OBJECTIVES: To gain further insight into the pathophysiology of hypoxia induced pulmonary hypertension and the resulting reduction in exercise capacity, we investigated if the reduction in hypoxic pulmonary vasoconstrictive response with corticosteroids or phosphodiesterase-5 inhibition improves exercise capacity. METHODS: A cardiopulmonary exercise test and echocardiography to estimate systolic pulmonary artery pressure were performed in 23 subjects with previous history of high altitude pulmonary edema, known to be associated with enhanced hypoxic vasoconstriction. Subjects were randomized to dexamethasone 8 mg twice a day, tadalafil 10 mg twice a day, or placebo (double-blinded), starting the day before ascent. MEASUREMENTS AND MAIN RESULTS: Measurements were performed at low and high (i.e., 4,559 m) altitude. Altitude exposure decreased maximum oxygen uptake and oxygen saturation, increased pulmonary artery pressure, and altered oxygen uptake kinetics. Compared with placebo, dexamethasone improved maximum oxygen uptake (% predicted 74 +/- 13%; tadalafil 63 +/- 13%, placebo 61 +/- 11%; P < 0.05), oxygen kinetics (mean response time 41 +/- 13 s; tadalafil 46 +/- 6 s, placebo 45 +/- 10 s; P < 0.05), and reduced the ventilatory equivalent for CO(2) (42 +/- 4; tadalafil 49 +/- 4, placebo 50 +/- 5; P < 0.01). Peak oxygen saturation did not differ significantly between the three groups (dexamethasone 66 +/- 7%, placebo 62 +/- 7%, tadalafil 69 +/- 5%; P = 0.08). During echocardiography at low-intensity exercise (40% of peak power), dexamethasone compared with placebo resulted in lower pulmonary artery pressure (47 +/- 9 mm Hg; tadalafil 57 +/- 11 mm Hg, placebo 68 +/- 23 mm Hg; P = 0.05) and higher oxygen saturation (74 +/- 7%; tadalafil 67 +/- 3%, placebo 61 +/- 20; P < 0.02). CONCLUSIONS: Corticosteroids, but not phosphodiesterase-5 inhibition, partially prevented the limitation of exercise capacity in subjects with intense hypoxic pulmonary vasoconstriction at high altitude.
Authors:
Manuel Fischler; Marco Maggiorini; Lorenz Dorschner; Johann Debrunner; Alain Bernheim; Stephanie Kiencke; Heimo Mairbäurl; Konrad E Bloch; Robert Naeije; Hans Peter Brunner-La Rocca
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial     Date:  2009-06-11
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  180     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-07     Completed Date:  2009-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  346-52     Citation Subset:  AIM; IM    
Affiliation:
Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland. manuel.fischler@usz.ch
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MeSH Terms
Descriptor/Qualifier:
Adult
Altitude Sickness / drug therapy*
Anti-Inflammatory Agents / adverse effects,  therapeutic use*
Carbolines / adverse effects,  therapeutic use*
Carbon Dioxide / blood
Dexamethasone / adverse effects,  therapeutic use*
Double-Blind Method
Echocardiography
Exercise Test / drug effects*
Female
Humans
Hypertension, Pulmonary / drug therapy
Lung / blood supply
Male
Middle Aged
Oxygen / blood
Phosphodiesterase Inhibitors / adverse effects,  therapeutic use*
Pulmonary Edema / drug therapy*
Pulmonary Wedge Pressure / drug effects
Vasoconstriction / drug effects
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Carbolines; 0/Phosphodiesterase Inhibitors; 0/tadalafil; 124-38-9/Carbon Dioxide; 50-02-2/Dexamethasone; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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