Ergogenic Effect of PDE-5 Inhibitors at Moderate Altitude

1. Purpose

The purpose of this research proposal is to evaluate the role of hypoxic pulmonary vasoconstriction (HPV) and the formation of arteriovenous anastomoses (shunts) in hypoxia and their effect on endurance exercise performance. The pulmonary vasodilator sildenafil will be used to reverse the effects of HPV during exercise. Large between-subject variability in exercise performance in hypoxia could be explained by similar variability in the HPV response. Elite and recreational athletes could benefit significantly from being aware of their HPV response to hypoxia and could alter their training accordingly based on this knowledge. The vasodilator sildenafil may provide a level playing field for those athletes who are compromised by a robust HPV response. 2. Hypothesis

A greater decline in exercise performance in acute moderate hypoxia (FIO2 = 0.16) will be correlated with a higher pulmonary artery pressure (PAP) during steady-state exercise and resting in hypoxia, increased arteriovenous anastomoses in hypoxia, and a lower hypoxic ventilatory response (HVR). These subjects will have significantly improved exercise performance in hypoxia with sildenafil administration. This increase in performance will be associated with reduced PAP and increases in cardiac output. 3. Justification

Professional athletic competitions are frequently held at moderate altitude: 1500-2999 meters, or a barometric pressure (PB) of 635-525 mmHg. These competitions include sports such as sky-running competitions and ski randonnée racing as well as Olympic competitions, for example the 1968 Mexico City Olympics, held at an altitude of 2,240 meters.

Reasons for holding a competition at altitude vary. Some event host cities have venues that are situated at moderate altitude. Winter events that require a significant snowpack, such as Nordic and alpine ski races, are routinely held above 1500 meters. Finally, some athletes such as track cyclists and long track speed skaters may seek out moderate altitude venues where decreased atmospheric pressure reduces aerodynamic drag.