Sildenafil Increased Exercise Capacity during Hypoxia at Low Altitudes and at Mount Everest Base Camp

Abstract

Sildenafil reduces hypoxic pulmonary hypertension at rest and during exercise while maintaining gas exchange and systemic blood pressure. To the authors' knowledge, sildenafil is the first drug shown to increase exercise capacity during severe hypoxia both at sea level and at high altitude.

Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity

“…[9][10][11] The phosphodiesterase-5 (PDE5) inhibitor sildenafil has been shown to improve pulmonary hemodynamics and exercise capacity in adults with group 1 pulmonary hypertension (PH) (defined by right heart catheterization [RHC] as a mean pulmonary artery pressure Ն 25 mmHg, a pulmonary artery occlusion pressure or a left ventricular end diastolic pressure Յ 15 mmHg, and an increased pulmonary vascular resistance) 12 : idiopathic or heritable pulmonary arterial hypertension (PAH), or PAH associated with connective tissue diseases or repaired congenital systemic to pulmonary shunts. 13 Further, sildenafil has been shown to improve exercise capacity in patients with left ventricular systolic dysfunction and pulmonary venous hypertension (defined via cardiac catheterization as a mean pulmonary artery pressure Ն 25 mmHg and a pulmonary artery occlusion pressure or a left ventricular end diastolic pressure Ն 15 mmHg) 14,15 and in healthy volunteers exposed to experimental hypoxia or high altitude, 16,17 suggesting a beneficial role of PDE5 inhibition in patients with group 2 PH (PH with left heart disease) and group 3 PH (PH associated with lung diseases and/or hypoxemia). PDE5 inhibition also prevents and reverses cardiac hypertrophy in mice exposed to chronic left ventricular pressure overload induced by transverse aortic constriction.…”

Can sildenafil improve physical performance at altitude? Current scientific evidence

“…Su papel como posible factor para aumentar el rendimiento en el ejercicio en condiciones de hipoxia está por demostrar, pero el uso de sildenafilo ha aumentado entre los montañeros, no como un fármaco preventivo del edema pulmonar de gran altitud, sino en la creencia de que podría ayudar a mejorar el rendimiento físico a gran altura geográfica. Varios estudios han tratado de abordar este tema, con resultados Since the work of Ghofrani et al 1 about the improvement of physical capacity during exercise in hypoxia conditions due to the use of sildenafil, 1 several studies have attempted to reproduce their findings. However, to date, there is still controversy over whether phosphodiesterase type 5 (PDE-5) inhibitor is a substance that can actually improve performance under hypoxic conditions.…”

“…These authors analyzed 5 articles, 3 of which have already been commented above. 1,14,29 It was evident that sildenafil administration is able to blunt the PAP increase induced by hypoxia exposure, but it does not improved SaO 2 and HR. Moreover, acute mountain sickness symptoms were not relieved by sildenafil treatment.…”

“…The first published study concerning the relationship between sildenafil, exercise and hypoxia was that of Ghofrani et al 1 These authors studied a group of 14 people (12 men and 2 women) who had previous experience in altitude exposure. Data from the participants were recorded at rest and during maximum incremental exercise tests (W peak ) in two different situations: (1) at an altitude of 171 m breathing through a mask of a hypoxic gas mixture with 10% fraction of oxygen for 2 h and (2) at an altitude of 5245 m after 8 days of ascent until Everest base camp.…”

“…14---16 VO 2max tends to diminish in direct proportion to the decrease in CaO 2 , which occurs as hypoxia increases. 17,18 Exercise exacerbates CaO 2 reduction due to the lower uptake of O 2 during gas exchanging in the lungs, 1,19 which may increase the risk of pulmonary edema, 11,20 especially in people predisposed to suffer this complications associated to rapid ascent. 21 Considering that the increase in PAP could be an important factor limiting performance during exercise in hypoxia, 22 sildenafil has been proposed as a potential ergogenic aid for physical activity in hypoxic conditions due to its possible benefits for athletic performance, and has been widely used.…”