title: Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension.
abstract: 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. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) 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.
authors.affiliation: Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, Université Paris, Bobigny, France. richalet@smbh.univ-paris13.fr
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Richalet
authors.forename: Pierre
authors.initials: P
authors.lastname: Gratadour
authors.forename: Paul
authors.initials: P
authors.lastname: Robach
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pham
authors.forename: Michèle
authors.initials: M
authors.lastname: Déchaux
authors.forename: Aude
authors.initials: A
authors.lastname: Joncquiert-Latarjet
authors.forename: Pascal
authors.initials: P
authors.lastname: Mollard
authors.forename: Julien
authors.initials: J
authors.lastname: Brugniaux
authors.forename: Jérémy
authors.initials: J
authors.lastname: Cornolo
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D000532:Altitude Sickness / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D004452:Echocardiography; D017079:Exercise Tolerance / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D000860:Hypoxia / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D010919:Placebos; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010919:Placebos; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases