Shortage of chemical fuel as a cause of fatigue: studies by nuclear magnetic resonance and bicycle ergometry.

The technique of nuclear magnetic resonance (n.m.r.) is briefly described to illustrate its use for estimating metabolite levels in vivo. Our studies of fatigue in anaerobic frog muscle at 4 degree C are described in relation to (a) force development, (b) speed of relaxation and (c) the switching on and off of glycolysis. Both (a) and (b) are closely related, though in different ways, to the concentrations of key metabolites. In contrast, (c) is not related to metabolite levels as such but to the events of contraction and relaxation. A special n.m.r. technique (saturation transfer) has been used to study the creatine kinase system in vivo. The results show that this system is highly active and is in equilibrium in resting muscle. The free [ADP] is consequently only a small fraction of that found by analysis of muscle extracts. Studies of human power production as a function of duration of exercise also indicate that it is shortage of chemical fuel that brings short- and medium-term exercise (0.1-10 min) to a halt. It is proposed to extend n.m.r. methods to human subjects in the near future. A working hypothesis to account for fatigue is suggested in which both the contractile system and the activating system play a part.