title: Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.
abstract: 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.
authors.affiliation: Exercise Physiology Laboratory, Clinical Studies Unit, GRECC, Veterans Affairs Palo Alto Health Care System, and Department of Medicine, Pulmonary and Critical Care, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hsu
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Barnholt
authors.forename: Nicolas K
authors.initials: NK
authors.lastname: Grundmann
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lin
authors.forename: Stewart W
authors.initials: SW
authors.lastname: McCallum
authors.forename: Anne L
authors.initials: AL
authors.lastname: Friedlander
mesh_terms: D000293:Adolescent; D000328:Adult; D000531:Altitude; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010807:Physical Endurance / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013450:Sulfones; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate