Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Ghofrani, HA; Reichenberger, F; Kohstall, MG; Mrosek, EH; Seeger, T; Olschewski, H; Seeger, W; Grimminger, F.
Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial.
Ann Intern Med. 2004; 141(3):169-177
Doi: 10.7326/0003-4819-141-3-200408030-00005
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-authors Med Uni Graz
- Olschewski Horst
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: Alveolar hypoxia causes pulmonary hypertension and enhanced right ventricular afterload, which may impair exercise tolerance. The phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. OBJECTIVE: To investigate the effects of sildenafil on exercise capacity under conditions of hypoxic pulmonary hypertension. DESIGN: Randomized, double-blind, placebo-controlled crossover study. SETTING: University Hospital Giessen, Giessen, Germany, and the base camp on Mount Everest. PARTICIPANTS: 14 healthy mountaineers and trekkers. MEASUREMENTS: Systolic pulmonary artery pressure, cardiac output, and peripheral arterial oxygen saturation at rest and during assessment of maximum exercise capacity on cycle ergometry 1) while breathing a hypoxic gas mixture with 10% fraction of inspired oxygen at low altitude (Giessen) and 2) at high altitude (the Mount Everest base camp). INTERVENTION: Oral sildenafil, 50 mg, or placebo. RESULTS: At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% (95% CI, 66.5% to 77.5%) at rest and 60.8% (CI, 56.0% to 64.5%) at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg (CI, 26.0 to 35.0 mm Hg) at rest to 42.9 mm Hg (CI, 35.6 to 53.5 mm Hg) during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (P = 0.005) and reduced systolic pulmonary artery pressure at rest (P < 0.001) and during exercise (P = 0.031). Of note, sildenafil increased maximum workload (172.5 W [CI, 147.5 to 200.0 W]) vs. 130.6 W [CI, 108.8 to 150.0 W]); P < 0.001) and maximum cardiac output (P < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (P = 0.003) and during exercise (P = 0.021) and increased maximum workload (P = 0.002) and cardiac output (P = 0.015). At high altitude, sildenafil exacerbated existing headache in 2 participants. LIMITATIONS: The study did not examine the effects of sildenafil on normoxic exercise tolerance. CONCLUSIONS: 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 3',5'-Cyclic-GMP Phosphodiesterase - antagonists and inhibitors
- Altitude - antagonists and inhibitors
- Anoxia - complications
- Blood Pressure - drug effects
- Cardiac Output - drug effects
- Cross-Over Studies - drug effects
- Double-Blind Method - drug effects
- Exercise Tolerance - drug effects
- Female - drug effects
- Humans - drug effects
- Hypertension, Pulmonary - drug therapy
- Male - drug therapy
- Oxygen - blood
- Phosphodiesterase Inhibitors - therapeutic use
- Piperazines - therapeutic use
- Placebos - therapeutic use
- Pulmonary Artery - physiology
- Vasodilator Agents - therapeutic use