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Published ahead of print on October 29, 2004, doi:10.1164/rccm.200406-804OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 3, February 2005, 275-281

A more recent version of this article appeared on February 1, 2005
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Submitted on June 25, 2004
Accepted on October 24, 2004

Sildenafil Inhibits the Altitude-induced Hypoxemia and Pulmonary Hypertension

Jean-Paul Richalet1*, Pierre Gratadour2, Paul Robach3, Isabelle Pham4, Michele Dechaux5, Aude Joncquiert-Latarjet6, Pascal Mollard6, Julien Brugniaux6, and Jeremy Cornolo6

1 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, EA2363, A.R.P.E., Universite Paris 13, Bobigny, France; Service de Physiologie et Explorations Fonctionnelles, Hopital Avicenne, AP-HP, Bobigny, France, 2 Service d'Anesthesie-reanimation, Hopital Hotel Dieu, Lyon, France, 3 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, EA2363, A.R.P.E., Universite Paris 13, Bobigny, France; Ecole Nationale de Ski et d'Alpinisme, Chamonix, France, 4 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, EA2363, A.R.P.E., Universite Paris 13, Bobigny, France; Service de Physiologie, Hopital Jean-Verdier AP-HP, Bondy, France, 5 Laboratoire de Physiologie, Hopital Necker, Paris, France, 6 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, EA2363, A.R.P.E., Universite Paris 13, Bobigny, France

* To whom correspondence should be addressed. 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, we examined the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects. Twelve subjects (sildenafil, SIL n=6; placebo, PLA n=6) were exposed for 6 days at 4,350m. Treatment (3 x 40mg / 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% vs sea level, p<0.01), then normalized in SIL (-6% vs sea level, ns) and remained elevated in PLA (+ 21% vs sea level, p<0.05). Pulmonary acceleration time decreased by 27% in PLA vs 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 VO2max was smaller in SIL than in PLA (p<0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, thus limiting the altitude-induced hypoxemia and decrease in exercise performance.
Key words: hypoxia, exercise, cardiac output, gas exchange




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