PT  - JOURNAL ARTICLE
AU  - Aldashev, A A
AU  - Kojonazarov, B K
AU  - Amatov, T A
AU  - Sooronbaev, T M
AU  - Mirrakhimov, M M
AU  - Morrell, N W
AU  - Wharton, J
AU  - Wilkins, M R
TI  - Phosphodiesterase type 5 and high altitude pulmonary hypertension
AID  - 10.1136/thx.2005.041954
DP  - 2005 Aug 01
TA  - Thorax
PG  - 683--687
VI  - 60
IP  - 8
4099  - http://thorax.bmj.com/content/60/8/683.short
4100  - http://thorax.bmj.com/content/60/8/683.full
SO  - Thorax2005 Aug 01; 60
AB  - Background: This study explored phosphodiesterase type 5 (PDE5) inhibition as a strategy for treating high altitude pulmonary arterial hypertension (HAPH). Methods: 689 subjects (313 men) of mean (SD) age 44 (0.6) years living above 2500 m were screened for HAPH by medical examination and electrocardiography, and 188 (27%) met the criteria for right ventricular hypertrophy. 44 underwent cardiac catheterisation and 29 (66%) had a resting mean pulmonary artery pressure (PAP) above 25 mm Hg. 22 patients with a raised mean PAP were randomised to receive sildenafil (25 or 100 mg) or matching placebo taken 8 hourly for 12 weeks. Results: At 3 months, patients on sildenafil 25 mg 8 hourly (n = 9) had a significantly (p = 0.018) lower mean PAP (−6.9 mm Hg) at the end of the dosing interval than those on placebo (n = 8) (95% CI −12.4 to −1.3). The treatment effect for sildenafil 100 mg 8 hourly (n = 5) compared with placebo was −6.4 mm Hg (95% CI −12.9 to 0.1). Both doses improved 6 minute walk distance, the lower dose by 45.4 m (95% CI 11.5 to 79.4; p = 0.011) and the higher dose by 40.0 m (95% CI 0.2 to 79.8; p = 0.049). Sildenafil was well tolerated. Necroscopic lung specimens from three subjects with HAPH showed abundant PDE5 in the muscular coat of remodelled pulmonary arterioles. Conclusions: PDE5 is an attractive drug target for the treatment of HAPH and a larger study of the long term effects of PDE5 inhibition in HAPH is warranted.