title: Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema.
abstract: BACKGROUND
  Whether pulmonary hypertension at high altitude limits exercise capacity remains uncertain.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland. manuel.fischler@usz.ch
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischler
authors.forename: Marco
authors.initials: M
authors.lastname: Maggiorini
authors.forename: Lorenz
authors.initials: L
authors.lastname: Dorschner
authors.forename: Johann
authors.initials: J
authors.lastname: Debrunner
authors.forename: Alain
authors.initials: A
authors.lastname: Bernheim
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kiencke
authors.forename: Heimo
authors.initials: H
authors.lastname: Mairbäurl
authors.forename: Konrad E
authors.initials: KE
authors.lastname: Bloch
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000188:drug therapy*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use*; D002245:Carbon Dioxide / Q000097:blood; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004452:Echocardiography; D005080:Exercise Test / Q000187:drug effects*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008168:Lung / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000188:drug therapy*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D000068581:Tadalafil; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D002245:Carbon Dioxide; D000068581:Tadalafil; D003907:Dexamethasone; D010100:Oxygen