Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia.
BACKGROUND
Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity. We tested the hypothesis that pulmonary vascular resistance (PVR) contributes to decreased exercise capacity in hypoxic healthy subjects.


METHODS
An incremental cycle ergometer cardiopulmonary exercise test and echocardiographic estimation of pulmonary artery pressure (Ppa) and cardiac output to calculate total PVR were performed in 11 healthy volunteers in normoxia and after 1 h of hypoxic breathing (12% O(2)). The measurements were performed in a random order at 1-week intervals after the receiving either a placebo or bosentan, following a double-blind randomized crossover design. Bosentan was administered twice a day for 3 days, 62.5 mg on the first day and 125 mg on the next 2 days.


RESULTS
Hypoxic breathing decreased the mean (+/- SE) pulse oximetric saturation (Spo(2)) from 99 +/- 1% to 3 +/- 1% and increased the mean PVR from 5.6 +/- 0.3 to 7.2 +/- 0.5 mm Hg/L/min/m(2), together with a decrease in mean maximum O(2) uptake (Vo(2)max) from 47 +/- 2 to 35 +/- 2 mL/kg/min. Bosentan had no effect on normoxic measurements and did not affect hypoxic Spo(2), but decreased PVR to 5.6 +/- 0.3 mm Hg/L/min/m(2) (p < 0.01) and increased Vo(2)max to 39 +/- 2 mL/kg/min (p < 0.01) in hypoxia. Bosentan therapy, on average, restored 30% of the hypoxia-induced decrease in Vo(2)max. Bosentan-induced changes in Ppa and Vo(2)max were correlated (p = 0.01).


CONCLUSIONS
We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects, and that bosentan therapy can prevent it.
Faoro
Vitalie
V
Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
Boldingh
Saskia
S
VU University Medical Center, Amsterdam, the Netherlands.
Moreels
Mickael
M
Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
Martinez
Sarah
S
Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium.
Lamotte
Michel
M
Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
Unger
Philippe
P
Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
Brimioulle
Serge
S
Department of Intensive Care, Erasme University Hospital, Brussels, Belgium.
Huez
Sandrine
S
Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
Naeije
Robert
R
Department of Physiology, Faculty of Medicine, Free University of Brussels, Belgium. Electronic address: rnaeije@ulb.ac.be.
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000077300:Bosentan; D002302:Cardiac Output; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D055815:Young Adult
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan