title: Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial.
abstract: Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE. By conducting a parallel-group double blind, randomized, placebo-controlled trial, we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness (AMS) during acclimatization to high altitude. Sixty-two healthy lowland volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research expedition were flown to La Paz, Bolivia (3650 m), and after 4-5 days acclimatization ascended over 90 min to 5200 m. The treatment group (n=20) received 50 mg sildenafil citrate three times daily. PASP was recorded by echocardiography at sea level and within 6 h, 3 days, and 1 week at 5200 m. AMS was assessed daily using the Lake Louise Consensus symptom score. On intention-to-treat analysis, there was no significant difference in PASP at 5200 m between sildenafil and placebo groups. Median AMS score on Day 2 at 5200 m was significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5; p=0.004) but there was no difference in prevalence of AMS between groups. Sildenafil administration did not affect PASP in healthy lowland subjects at 5200 m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil. Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER: NCT00627965.
authors.affiliation: Mitochondrial Research Group, Medical School, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom. matthew.bates@ncl.ac.uk
authors.forename: Matthew G D
authors.initials: MG
authors.lastname: Bates
authors.forename: A A Roger
authors.initials: AA
authors.lastname: Thompson
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Baillie
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Sutherland
authors.forename: John B
authors.initials: JB
authors.lastname: Irving
authors.forename: Nikhil
authors.initials: N
authors.lastname: Hirani
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000150:complications / Q000503:physiopathology; D001794:Blood Pressure; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000503:physiopathology; D057194:Intention to Treat Analysis; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D013599:Systole; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate