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.

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

“…However, data are not categorical, both at rest and during exercise. The arterial blood pressure (systolic, diastolic and mean) 1,18,29,31,32 and systolic volume 18,31,32 were almost not affected. Lung function parameters (ventilation, tidal volume, respiratory rate and respiratory exchange ratio) were unaffected by the drug 14,15,18,30 .…”

“…Lung function parameters (ventilation, tidal volume, respiratory rate and respiratory exchange ratio) were unaffected by the drug 14,15,18,30 . Finally, the exercise values such as W peak 1,14,15,18,29,31,32 or VO 2max 14,29 are not conclusive at all to affirm that sildenafil significantly improves performance during exposure to acute hypoxia, regardless its normobaric or hypobaric nature.…”

“…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.…”

“…Richalet et al 29 exposed 12 healthy men (not acclimated to altitude with a moderate physical condition) for 6 days at an altitude of 4350 m. The treatment was to take one dose of 40 mg of sildenafil or placebo, three times a day (8:00 am; 2:00 pm and 8:00 pm). Measurements of systemic and pulmonary blood pressure, CO and SaO 2 , were taken during 12 days, 3 times a day.…”