Researchers at Rice and Harvard link metabolism to muscle fatigue in the body

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Why exercising muscles tire when needed most

Researchers at Rice and Harvard link metabolism to muscle fatigue in the body

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.

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.

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    Editor’s note: A photo of a cyclist can be
downloaded for publication at the following link, courtesy of Rice
University: http://www.rice.edu/media/cycle.html