Journal of Applied Physiology AJP: Lung Cellular and Molecular Physiology
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J Appl Physiol 100: 2031-2040, 2006. First published February 2, 2006; doi:10.1152/japplphysiol.00806.2005
8750-7587/06 $8.00
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Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia

Andrew R. Hsu,1 Kimberly E. Barnholt,1 Nicolas K. Grundmann,1 Joseph H. Lin,2 Stewart W. McCallum,3 and Anne L. Friedlander1,4

1Exercise Physiology Laboratory, Clinical Studies Unit, Veterans Affairs Palo Alto Health Care System, 2Department of Medicine, Pulmonary and Critical Care, Stanford University School of Medicine, 3Department of Urology, Stanford University Medical Center, and 4Geriatric Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California

Submitted 7 July 2005 ; accepted in final form 30 January 2006

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, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three 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% work capacity: 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 before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, 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 nonresponders, 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.

phosphodiesterase-5 inhibitor; simulated altitude; Viagra; Physioflow; pulmonary hypertension


Address for reprint requests and other correspondence: A. L. Friedlander, Exercise Physiology Laboratory, Clinical Studies Unit, GRECC, 182B, MB2, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304 (e-mail: friedlan{at}stanford.edu)




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