Theophylline delays skeletal muscle fatigue during progressive exercise

In this study, 31P nuclear magnetic resonance spectroscopy (NMRS) was used to examine the effect of theophylline on human forearm muscle metabolism during progressive exercise. Six healthy men (37 +/- 14 yr of age) were assigned to either a control (CTRL) group (n = 3), or a theophylline treatment (THEO) group (n = 3). Each subject performed two dynamic wrist flexion exercise tests to fatigue, with at least 72 h separating each trial. The THEO group repeated the protocol after receiving 300 mg of sustained-release theophylline every 12 h. 31P spectra were acquired every 36 s throughout exercise, and the relative contributions of the phosphate metabolites and pH were determined. Power output at the onset, or threshold of intracellular acidosis (IT), was identified for each subject from changes in phosphocreatine (PCr) metabolism and pH. Power at maximal exercise and at the IT was found to be reproducible in the CTRL group. After theophylline administration, the maximal power attained by the THEO group increased significantly by 19% (p < 0.05), from 2.25 +/- 0.2 to 2.68 +/- 0.15 W. A similar trend occurred in the onset of the IT, which was also prolonged by 19%, from 1.33 +/- 0.18 to 1.58 +/- 0.22 W. Therapeutic concentrations of theophylline significantly increased the endurance of the forearm musculature, apparently by delaying the onset of intracellular metabolic acidosis. These findings suggest an enhancement of oxidative capacity of the muscle.