Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema.
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.
Fischler
Manuel
M
Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland. manuel.fischler@usz.ch
Maggiorini
Marco
M
Dorschner
Lorenz
L
Debrunner
Johann
J
Bernheim
Alain
A
Kiencke
Stephanie
S
Mairbäurl
Heimo
H
Bloch
Konrad E
KE
Naeije
Robert
R
Brunner-La Rocca
Hans Peter
HP
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
D000893:Anti-Inflammatory Agents; D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D002245:Carbon Dioxide; D000068581:Tadalafil; D003907:Dexamethasone; D010100:Oxygen