Decreased pulmonary artery pressure by oral sildenafil ingestion at mild altitude and during exercise in air pollution increases exercise performance

Code: 07E04KR

Sildenafil (phosphodiesterase-5 inhibitor) is recognized as treatment for pulmonary hypertension and erectile dysfunction. Ingestion at therapeutic dose shows profound improvement in pulmonary artery pressure, cardiac output, VO2peak, and exercise capacity at hypoxic conditions; at sea level breathing 10% O2 and at Mount Everest base camp (>5,000 m) in subjects free of lung disease. Olympic Nordic venues are often at mild altitude; the Salt Lake Olympic Nordic venue is approximately 1,700 m and the Turin venue is at 1,540 m altitude. Although the Vancouver Nordic venue is at 860 m altitude, significant reductions in VO2peak (-5.9%) and maximal 5-min cycle ergometry performance (total kJ, -3.6%) has been documented at simulated 580 m altitude. Therefore, further studies are needed to characterize potential ergogenic effects of sildenafil at mild altitude. Likewise, short-term inhalation of concentrated ambient air particles (PM) promotes vasoconstriction of small pulmonary arteries and produces pathologic features consistent with pulmonary hypertension. We recently found that breathing high levels of combustion-derived PM during exercise caused a significant (~5%) decrease in 6 min cycle ergometry work output. Since the pulmonary vasculature is a target for effects of ambient PM from fossil fuel combustion, oral sildenafil may enhance performance at ice rink venues (resurfaced with fossil-fueled machines) and at the upcoming Beijing and London Olympics venues which are likely to have high levels of PM. The aims of this project are to determine if a therapeutic dose of sildenafil enhances exercise performance and aerobic capacity 1) in high PM pollution and 2) at mild simulated altitude consistent with Olympic venue altitudes, 3) elucidate a potential mechanism, and 4) confirm measurement of sildenafil and metabolites in plasma and urine. These studies will provide evidence detailing performance enhancement from prior-to-competition ingestion of oral sildenafil at 1) high air pollution venues and at 2) mild altitude.

Main Findings

Exercise performance in this study was not significantly decreased in high particulate matter (PM) air for placebo or treatment groups. Although mean performance was 10 kJ lower for high pollution exercise, individual variability did not allow statistical significance. However, when data was analyzed after separating individuals into responders and non-responders as previously done in other studies, significant improvement in performance was noted for those who had a positive response to sildenafil. We further identified increased in mean pulmonary artery pressure (PAP) 1 h after high pollution exercise, but not after exercise in clean air that was associated with decreased performance. Ingestion of 50 mg sildenafil blunted the observed increase in PAP after high PM exposure exercise. The pulmonary artery pressures we recorded were normal for healthy young males, even after the increases recorded from high PM exposure exercise. However, the 18% change in PAP observed from high pollution exercise was significant (p=0.05) and likely affected exercise performance. In conclusion, oral ingestion of sildenafil citrate blunted the increase in pulmonary artery pressure resulting from exercise in high emissions particulate and was likely responsible for a noted improved exercise performance in the majority of subject in this study. Given the likelihood of international competitions being held in high emission environments, sildenafil citrate could provide an unfair advantage for some.