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Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema.
Am J Respir Crit Care Med. 2009 Aug 15; 180(4):346-52.AJ

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.

Authors+Show Affiliations

Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland. manuel.fischler@usz.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19520908

Citation

Fischler, Manuel, et al. "Dexamethasone but Not Tadalafil Improves Exercise Capacity in Adults Prone to High-altitude Pulmonary Edema." American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 4, 2009, pp. 346-52.
Fischler M, Maggiorini M, Dorschner L, et al. Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema. Am J Respir Crit Care Med. 2009;180(4):346-52.
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), 346-52. https://doi.org/10.1164/rccm.200808-1348OC
Fischler M, et al. Dexamethasone but Not Tadalafil Improves Exercise Capacity in Adults Prone to High-altitude Pulmonary Edema. Am J Respir Crit Care Med. 2009 Aug 15;180(4):346-52. PubMed PMID: 19520908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexamethasone but not tadalafil improves exercise capacity in adults prone to high-altitude pulmonary edema. AU - Fischler,Manuel, AU - Maggiorini,Marco, AU - Dorschner,Lorenz, AU - Debrunner,Johann, AU - Bernheim,Alain, AU - Kiencke,Stephanie, AU - Mairbäurl,Heimo, AU - Bloch,Konrad E, AU - Naeije,Robert, AU - Brunner-La Rocca,Hans Peter, Y1 - 2009/06/11/ PY - 2009/6/13/entrez PY - 2009/6/13/pubmed PY - 2009/8/25/medline SP - 346 EP - 52 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 180 IS - 4 N2 - 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. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/19520908/Dexamethasone_but_not_tadalafil_improves_exercise_capacity_in_adults_prone_to_high_altitude_pulmonary_edema_ L2 - http://www.atsjournals.org/doi/full/10.1164/rccm.200808-1348OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -