In this study we examined the time course of changes in the plasma concentr
ation of oxypurines [hypoxanthine (Hx), xanthine and urate] during prolonge
d cycling to fatigue. Ten subjects with an estimated maximum oxygen uptake
((V) over dot O-2max) of 54 (range 47-67) ml . kg(-1) . min(-1) cycled at [
mean(SEM)] 74(2)% of (V) over dot O-2max until fatigue [79(8) mini. Plasma
levels of oxypurines increased during exercise, but the magnitude and the t
ime course varied considerably between subjects. The plasma concentration o
f Hx ([Hx]) was 1.3 (0.3) mu mol/l at rest and increased eight fold at fati
gue. After 60 min of exercise plasma [Hx] was >10 mu mol/l in four subjects
, whereas in the remaining five subjects it was <5 mu mol/l. The muscle con
tents of total adenine nucleotides (TAN = ATP + ADP + AMP) and inosine mono
phosphate (IMP) were measured before and after exercise in five subjects. S
ubjects with a high plasma [Hx] at fatigue also demonstrated a pronounced d
ecrease in muscle TAN and increase in IMP. Plasma [Hx] after 60 min of exer
cise correlated significantly with plasma concentration of ammonia ([NH3],
r = 0.90) and blood lactate (r = 0.66). Endurance, measured as time to fati
gue, was inversely correlated to plasma [Hx] at 60 min(r = -0.68, P < 0.05)
but not to either plasma [NH3] or blood lactate. It is concluded that duri
ng moderate-intensity exercise, plasma [Hx] increases, but to a variable ex
tent between subjects. The present data suggest that plasma [Hx] is a marke
r of adenine nucleotide degradation and energetic stress during exercise. T
he potential use of plasma [Hx] to assess training status and to identify o
vertraining deserves further attention.