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Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema


Fischler, M; Maggiorini, M; Dorschner, L; Debrunner, J; Bernheim, A; Kiencke, S; Mairbäurl, H; Bloch, K E; Naeije, R; Brunner-La Rocca, H P (2009). Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema. American Journal of Respiratory and Critical Care Medicine, 180(4):346-352.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:15 August 2009
Deposited On:24 Jan 2010 08:35
Last Modified:05 Apr 2016 13:48
Publisher:American Thoracic Society
ISSN:1073-449X
Publisher DOI:https://doi.org/10.1164/rccm.200808-1348OC
PubMed ID:19520908
Permanent URL: https://doi.org/10.5167/uzh-28317

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