Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
Randomized, Controlled Trial of Regular Sildenafil Citrate in the Prevention of Altitude Illness
The purpose of this study is to determine whether regular oral use of sildenafil citrate can
 prevent or attenuate high altitude illnesses.
High altitude pulmonary oedema (HAPE) is a life-threatening non-cardiogenic lung injury
 precipitated by exaggerated pulmonary hypertension. The incidence of this rapidly progressive
 illness, among the estimated 40 million visitors to high altitude each year, may be as high
 as 0.5-2.0%. The pathogenesis of HAPE is multifactorial and may include impaired clearance of
 alveolar fluid, increased pulmonary vascular permeability and genetic susceptibility.
 Elevated pulmonary artery pressure (PAP) caused by hypoxic pulmonary vasoconstriction (HPV)
 is a key prerequisite for the development of HAPE and thus the reduction of PAP is paramount
 in the prophylaxis and treatment of this devastating illness.

 Nitric oxide (NO) is thought to play an important role in the exaggerated HPV that
 characterises HAPE. NO, constitutively produced in the lung by the enzyme endothelial nitric
 oxide synthase (eNOS), increases intracellular cGMP in pulmonary vascular smooth muscle and
 activates cGMP-dependent protein kinase, ultimately leading to a reduction in intracellular
 calcium and smooth muscle relaxation. HAPE-susceptible individuals exhale less NO during both
 normobaric and hypobaric hypoxia suggesting that a deficiency of NO synthesis may predispose
 to HAPE. At high altitude, inhaled NO causes a significantly greater reduction in the
 systolic PAP of HAPE-susceptible individuals compared to its effect on the PAP of
 HAPE-resistant subjects, but the administration of NO would be impractical in the field. Most
 recently, work has concentrated on another target in the NO pathway.

 Sildenafil citrate is an orally active, potent and selective phosphodiesterase type-5 (PDE-5)
 inhibitor. PDE-5 is the predominant enzyme responsible for degradation of cGMP in the lung.
 In a small sea level study, Zhao et al. demonstrated that pre-treatment with sildenafil
 nearly completely abolished the pulmonary vasopressor response to breathing hypoxic gas in
 healthy humans. More recently, studies at altitude have also shown reductions in pulmonary
 artery systolic pressure (PASP) in subjects taking sildenafil at high altitude.

 One potential problem with the use of sildenafil at altitude is that PDE-5 inhibitors may
 worsen symptoms of acute mountain sickness (AMS). Headache is a defining symptom in AMS and
 is a prominent side effect of sildenafil.

 We conducted a double-blind placebo-controlled randomised trial to assess the effect of
 regular sildenafil administration on PASP and Lake Louise AMS score at an altitude of 5200 m.
Inclusion Criteria:

 -  Participant in Apex 2 high altitude expedition

 Exclusion Criteria:

 -  Previous history of high altitude pulmonary edema