Fatigue of mammalian skeletal muscle in situ during repetitive contractions.

When the gastrocnemius-plantaris muscle group of the dog is stimulated to contract repetitively for 30 min at frequencies high enough to generate VO2 levels at or near VO2 max, VO2 and mechanical performance decline with time. This decline with time is fatigue, and it occurs during twitch and tetanic contractions that are isometric or isotonic. There is oxidation of the mitochondrial electron transport system, and net lactic acid output is transient, ending after 20 min of contractions. Energy and substrate stores and intracellular pH are only moderately changed and do not appear to be well correlated with the development of fatigue. Blood flow through the muscle is well correlated with the development of fatigue and decreases as fatigue develops in a manner that keeps the blood arteriovenous O2 difference nearly constant. Changing the blood flow alters the rate of development of fatigue as an inverse relation, and this response does not appear to be related to changes in the availability of O2 in the mitochondria. Nerve-muscle transmission of excitation does not seem to be involved in the development of fatigue. Excitation-contraction coupling is well accepted to be at least part of the genesis of the development of fatigue. Metabolic limitations and control may affect excitation-contraction coupling by one or more changes in the internal environment. Blood flow affects this system by an unknown mechanism. The role of blood flow in fatigue deserves further consideration.