Muscle fatigue in McArdle's disease studied by ³¹P-NMR: Effect of glucose infusion

In muscle phosphorylase deficiency (McArdle's disease) there is an abnormally rapid fatigue during strenuous exercise. Increasing substrate availability to working muscle can improve exercise tolerance but the effect on muscle energy metabolism has not been studied. Using phosphorus-31 nuclear magnetic resonance (³¹P-NMR) we examined forearm muscle ATP, phosphocreatine (PCr), inorganic phosphate (P(i)) and pH in a McArdle patient (MP) and two healthy subjects (HS) at rest and during intermittent maximal effort handgrip contractions under control conditions (CC) and during intravenous glucose infusion (GI). Under CC, MP gripped to impending forearm muscle contracture in 130 s with a marked decline in muscle PCr and a dramatic elevation in P(i). During GI MP exercised easily for >420 s at higher tensions and with attenuated PCr depletion and P(i) accumulation. In HS, muscle PCr and P(i) changed more modestly and were not affected by GI. In MP and HS, ATP changed little or not at all with exercise. The results suggest that alterations in the levels of muscle PCr and P(i) but not ATP are involved in the muscle fatigue in McArdle's disease and the improved exercise performance during glucose infusion.