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1 Exercise Physiology Laboratory, Clinical Studies Unit, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
2 Department of Medicine, Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA
3 Department of Urology, Stanford University, Palo Alto, CA, USA
4 Exercise Physiology Laboratory, Clinical Studies Unit, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
* To whom correspondence should be addressed. E-mail: friedlan{at}stanford.edu.
Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output (Q), arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained males performed 1 practice and 3 experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set work rate portion (55% Wattspeak: 1 h SL, 30 min HA) followed immediately by a time-trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h prior to exercise in a randomly, counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% O2) 1 h prior to exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), Q, and SaO2 during set work rate exercise. Sildenafil lowered 6 km time-trial time by 15% (P < 0.05). Sao2 was also higher during the time trial (P < 0.05) in response to sildenafil, despite higher work rates. Post-hoc analyses revealed two subject groups, sildenafil responders and non-responders, who improved time-trial performance by 39% (P < 0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.
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