The cause of muscle fatigue during intense exercise is linked directly to the muscle’s reliance on anaerobic metabolism for force production, according to a new study by researchers at Rice and Harvard universities.

Published in the November issue of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, the study implicates the reliance on anaerobic energy release as a key factor in the onset of muscle fatigue and impaired exercise performance. While the mechanism of how anaerobic pathways might impair force production remains under active investigation, the new results suggest that the mechanisms of muscular fatigue in the body are probably similar to the mechanisms being discovered in laboratory research on cell and tissue samples.

The researchers had six males perform 15 all-out sprints on a stationary cycle at varying pedal forces, which meant varying muscle-force requirements. Besides conventional cycling, the researchers also had the study participants perform similar all-out sprints with only one leg while the unused leg rested on an adjacent stool. Although this approach may seem unorthodox, the Rice-Harvard group knew from previous work that the metabolic pathways providing the chemical energy necessary for contraction would differ appreciably during the one- and two-legged conditions, said principal investigator Peter Weyand, assistant professor in kinesiology at Rice.

During exercise, muscles continuously break down and resynthesize the chemical ATP (adenosine triphosphate), which serves as the immediate source of energy for muscle contractions. During less vigorous muscular activity, essentially all of the ATP needed for muscular contraction can be provided via aerobic pathways that utilize oxygen delivered via the bloodstream. The aerobic pathways allow moderate levels of force to be generated without fatigue for prolonged periods, but can only support modest levels of muscular activity, due to the upper limits on how rapidly blood and oxygen can be supplied to the working muscles by the heart. Consequently, during more vigorous exercise, such as sprinting or lifting heavy loads or weights, the aerobic provision of ATP is supplemented by anaerobic pathways that do not rely on oxygen delivery. While the anaerobic pathways provide ATP very rapidly, their capacity is finite and must be replenished after each bout.

The researchers knew that the rates of oxygen delivery, aerobic metabolism and the amount of “aerobic” muscle force generated would be much greater in the active leg under the one-legged condition simply because the heart and circulation can provide relatively more blood and oxygen when only one limb is active. Thus, the researchers were confident that a much greater fraction of the muscle force required would be provided via chemical energy that came from aerobic pathways for all of the one-legged versus the two-legged sprint trials.

The cyclists were asked to pedal stationary cycles for a series of sprints at the rate of 100 revolutions per minute, continuing an all-out effort until they could no longer maintain this speed for at least five seconds. The researchers simultaneously measured the forces the subjects applied to the pedals, the amount of oxygen they inhaled and the electrical activity of the thigh muscles used to apply pedal force. Electrodes were attached to the skin of the thigh to measure electrical activity in the leg muscles.

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Weyand and colleagues found that the electrical activity of the leg muscles increased throughout each workout. Such increases are common during fatiguing contractions as individual muscle fibers develop less force over time. “Under these conditions, the exercise can be continued only if the individual activates new, unfatigued muscle to augment the impaired force from the muscle fibers originally activated,” Weyand said. “The increase in electrical signals from the active muscles can be used to indirectly assess the amount of fatigue the muscles are experiencing.”

As the researchers had hypothesized, the subjects had much higher peak rates of aerobic metabolism and pedal forces per leg when they used just one leg. During both the one- and two-legged sprints performed at pedal forces greater than those that could be supported via the aerobic pathways, the researchers observed progressive increases in electrical activity in the thigh muscles. “This indicates that new muscle fibers were being recruited throughout each sprint trial to provide the muscle force necessary to maintain a constant pedal force required by the sprint,” Weyand said.

Due to the lesser pedal forces supported via the aerobic pathways during two-legged cycling, the onset of compensatory muscle recruitment occurred at lower thresholds of pedal and muscle force in this mode. Similarly, at equivalent pedal forces, the rates of increase in compensatory electrical activity in the muscles were greater during two-legged than one-legged sprint cycling. “We attribute these between-mode differences in the rates at which muscles become fatigued and additional muscle is recruited to the greater reliance on anaerobic pathways of ATP resynthesis for force production during two-legged cycling versus one-legged cycling,” Weyand said.

“Although scientists have observed similar fatiguing patterns of electrical activity in people holding heavy objects, performing calisthenics and fine-motor tasks, muscular force decrements had not been shown previously to be so closely linked to the anaerobic pathways of ATP resynthesis,” he said.

Weyand suggested that the study raises the possibility that relying on the anaerobic pathways for chemical energy might be intrinsically fatiguing. “Experts focusing on locomotion and whole-body activities have attributed performance limitations during running, cycling, swimming and other athletic activities that involve many muscles simultaneously to the maximum rates at which ATP can be resynthesized from all pathways and not to an impaired ability of skeletal muscles to produce force during contraction,” he said. “Although bicep curls might not induce huffing, puffing and the same level of discomfort incurred by an all-out sprint, your muscles might not know the difference.”

Weyand’s coauthors on the paper are Matthew Bundle, formerly a Rice research fellow in the Department of Kinesiology and now an assistant professor at the University of Wyoming; and Carrie Ernst, Matthew Bellizzi and Seth Wright, all at Harvard.

The study was funded by the U.S. Army Medical and Materiel Command, the National Institutes of Health and the National Research Council.