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Published ahead of print on October 29, 2004, doi:10.1164/rccm.200406-804OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 275-281, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200406-804OC

Original Article

Sildenafil Inhibits Altitude-induced Hypoxemia and Pulmonary Hypertension

Jean-Paul Richalet, Pierre Gratadour, Paul Robach, Isabelle Pham, Michèle Déchaux, Aude Joncquiert-Latarjet, Pascal Mollard, Julien Brugniaux and Jérémy Cornolo

Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, Université Paris 13, Bobigny; Service de Physiologie et Explorations Fonctionnelles, hôpital Avicenne, Bobigny; Service d'Anesthésie-réanimation, hôpital Hôtel Dieu, Lyon; Service de Physiologie, hôpital Jean-Verdier, Bondy; Ecole Nationale de Ski et d'Alpinisme, Chamonix; Laboratoire de Physiologie, hôpital Necker, Paris, France

Correspondence and requests for reprints should be addressed to Jean-Paul Richalet, M.D., Ph.D., UFR. SMBH, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France. E-mail: richalet{at}smbh.univ-paris13.fr

Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (–6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. PaO2 was higher and alveolar-arterial difference in O2 lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O2 consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.

Key Words: cardiac output • exercise • gas exchange • hypoxia




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