Effects of sildenafil on exercise capacity in hypoxic normal subjects.
The phosphodiesterase-5 inhibitor sildenafil has been reported to improve hypoxic exercise capacity, but the mechanisms accounting for this observation remain incompletely understood. Sixteen healthy subjects were included in a randomized, double-blind, placebo-controlled, cross-over study on the effects of 50-mg sildenafil on echocardiographic indexes of the pulmonary circulation and on cardiopulmonary cycle exercise in normoxia, in acute normobaric hypoxia (fraction of inspired O2, 0.1), and then again after 2 weeks of acclimatization at 5000 m on Mount Chimborazo (Ecuador). In normoxia, sildenafil had no effect on maximum VO2 or O2 saturation. In acute hypoxia, sildenafil increased maximum VO2 from 27 +/- 5 to 32 +/- 6 mL/min/kg and O2 saturation from 62% +/- 6% to 68% +/- 9%. In chronic hypoxia, sildenafil did not affect maximum VO2 or O2 saturation. Resting mean pulmonary artery pressure increased from 16 +/- 3 mmHg in normoxia to 28 +/- 5 mmHg in normobaric hypoxia and 32 +/- 6 mmHg in hypobaric hypoxia. Sildenafil decreased pulmonary vascular resistance by 30% to 50% in these different conditions. We conclude that sildenafil increases exercise capacity in acute normobaric hypoxia and that this is explained by improved arterial oxygenation, rather than by a decrease in right ventricular afterload.
Faoro
Vitalie
V
Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
Lamotte
Michel
M
Deboeck
Gael
G
Pavelescu
Adriana
A
Huez
Sandrine
S
Guenard
Hervé
H
Martinot
Jean-Benoît
JB
Naeije
Robert
R
D000328:Adult; D000531:Altitude; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D012016:Reference Values; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013990:Tidal Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate