Pulmonary artery pressure limits exercise capacity at high altitude

Abstract

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR).Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg?day -1 for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V9O 2 ,max). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p,0.001), and partly restored V9O 2 ,max, by 30 % in acute hypoxia (p,0.001) and 10% in chronic hypoxia (p,0.05). Sitaxsentan-induced changes in PVR and V9O 2 ,max were correlated (p50.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake.Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.

Improvement in lung diffusion by endothelin A receptor blockade at high altitude

“…Thus interefering with endothelin-1 signaling could potentially affect lung diffusing capacity by pulmonary and renal fluid retention. However, the intake of the endothelin A receptor blocker sitaxsentan did not affect the renal handing of sodium and water in healthy volunteers at 5,050 m (34). In the present study, the observed effects of sitaxsentan are thus most likely related to a specific pulmonary hemodynamic effect.…”

“…The echocardiography and the incremental cycle ergometer CPET were performed as previously reported (34). The hemodynamic measurements relevant to the present study were cardiac output (Q) and pulmonary artery pressure (PAP), estimated, respectively, from the left ventricular outflow tract time-velocity integral and the maximal velocity of tricuspid regurgitation (TRmax).…”

“…Part of this improvement in exercise capacity could have been related to improved lung diffusing capacity, either as a consequence of decreased pulmonary vascular pressures (34) or inhibition of some negative effect of endothelin-1 at the alveolocapillary membrane (32). The latter would be unlikely after sitaxsentan, since there is experimental evidence that endothelin inhibits the alveolar epithelial transport of sodium and water but through the specific interaction with endothelin B receptors (5,11).…”

“…We more recently reported on an improvement in exercise capacity that was correlated to decreased pulmonary vascular resistance (PVR) by the intake of the endothelin A receptor blocker sitaxsentan in lowlanders after a 1-wk hike to the altitude of 5, 050 m (34). Part of this improvement in exercise capacity could have been related to improved lung diffusing capacity, either as a consequence of decreased pulmonary vascular pressures (34) or inhibition of some negative effect of endothelin-1 at the alveolocapillary membrane (32).…”

Can sildenafil improve physical performance at altitude? Current scientific evidence

“…17,18 Exercise exacerbates CaO 2 reduction due to the lower uptake of O 2 during gas exchanging in the lungs, 1,19 which may increase the risk of pulmonary edema, 11,20 especially in people predisposed to suffer this complications associated to rapid ascent. 21 Considering that the increase in PAP could be an important factor limiting performance during exercise in hypoxia, 22 sildenafil has been proposed as a potential ergogenic aid for physical activity in hypoxic conditions due to its possible benefits for athletic performance, and has been widely used. 23---27 This could be of especial interest in some countries, such as Andean or central Asia plateaus, where many professional athletes and football and other collective sport teams have to perform or play in locations higher than 2500 m. Finally, sildenafil use has also been promoted under the name of ''Vitamin V'' in some Internet forums because it supposedly improves muscle hypertrophy in bodybuilders and fitness enthusiasts.…”