Plasma hypoxanthine and ammonia in humans during prolonged exercise

In this study we examined the time course of changes in the plasma concentration of oxypurines hypoxanthine (Hx), xanthine and urate] during prolonged cycling to fatigue. Ten subjects with an estimated maximum oxygen uptake (VO2(max)) of 54 (range 47-67) ml x kg(-1) x min(-1) cycled at mean (SEM)] 74 (2)% of VO2(max) until fatigue 79 (8) min]. Plasma levels of oxypurines increased during exercise, but the magnitude and the time course varied considerably between subjects. The plasma concentration of Hx (Hx]) was 1.3 (0.3) micromol/l at rest and increased eight fold at fatigue. After 60 min of exercise plasma Hx] was >10 micromol/l in four subjects, whereas in the remaining five subjects it was <5 micromol/l. The muscle contents of total adenine nucleotides (TAN = ATP+ADP+AMP) and inosine monophosphate (IMP) were measured before and after exercise in five subjects. Subjects with a high plasma Hx] at fatigue also demonstrated a pronounced decrease in muscle TAN and increase in IMP. Plasma Hx] after 60 min of exercise correlated significantly with plasma concentration of ammonia (NH(3)], r = 0.90) and blood lactate (r = 0.66). Endurance, measured as time to fatigue, was inversely correlated to plasma Hx] at 60 min (r = -0.68, P < 0.05) but not to either plasma NH(3)] or blood lactate. It is concluded that during moderate-intensity exercise, plasma Hx] increases, but to a variable extent between subjects. The present data suggest that plasma Hx] is a marker of adenine nucleotide degradation and energetic stress during exercise. The potential use of plasma Hx] to assess training status and to identify overtraining deserves further attention.