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Dexamethasone But Not Tadalafil Improves Exercise Capacity in Adults Prone to High-Altitude Pulmonary Edema

¹ Intensive Care Unit DIM, University Hospital Zurich, Zurich, Switzerland; ² Division of Cardiology, University Hospital Basel, Basel, Switzerland; ³ Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany; ⁴ Division of Pneumology, University Hospital Zurich, Zurich, Switzerland; and ⁵ Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium

Correspondence and requests for reprints should be addressed to Manuel Fischler, M.D., Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland. E-mail: manuel.fischler{at}usz.ch

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 CO₂ (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.

Key Words: high-altitude pulmonary edema • cardiopulmonary exercise test • glucocorticoids • phosphodiesterase-5 inhibitor • pulmonary hypertension

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Whether pulmonary hypertension at high altitude limits exercise capacity remains uncertain. Sildenafil increases exercise capacity during hypoxia. What This Study Adds to the Field Dexamethasone, but not tadalafil, may improve exercise capacity during hypoxia in HAPE-susceptible mountaineers. Pulmonary circulation plays a central role in reduced exercise capacity at high altitude.