Peripheral excitatory and contractile mechanisms underlying fatigue resistance of human skeletal muscle.
Experiments have been designed to investigate the physiological factors
influencing the interrelationship between excitation and force generation that may
counteractt he processesle ading to a decline in force (fatigue) during stimulatedi sometric
contractions of the human adductor pollicis in vivo. Indices of isometric force, relaxation
and contraction rates and evoked compound muscle action potentials (CMAP) were
measured during defined patterns of stimulated activity (via the motor nerve). A
computerized stimulator controller for precise generation of trains of electrical impulses
was developed for this purpose. Forces generated at different frequencies were
reproducible on separate occasions.
Using an ascending frequency stimulation protocol (1-100Hz) the relationship
between force decline and excitation (measured as the amplitude of the surface evoked
CMAP) appeared to be dependent on stimulation frequency during ischaemic and nonoccluded
activity. At high frequencies (50-100Hz), a `safety factor' was apparent,
allowing preservation of force despite a marked fall in excitation, whereas at low
frequencies (1-10Hz) force initially potentiated and then declined in excess of excitation.
Maximum relaxation rate was reduced at all stimulation frequencies and was independent
of stimulation frequency.
Contractile activity performed was shown to be linearly related to maximum
relaxation rate over a frequency range of 20-100Hz for up to 30max. seconds. Contractile
activity performed was therefore used as a measure of the metabolic cost of a contraction.
Force failure appeared to depend upon the numbers of stimuli delivered, independent of
frequency, rather than on contractile activity performed, suggesting that
electrophysiological factors are of importance in contributing to fatigue.
Further studieso n CMAP characteristicsd emonstrateda broadeningo f the action
potential, reflecting a slowing of conduction velocity, which is thought to lead to `runin'
of action potentials, and hencet he reduction of CMAP amplitude associatedw ith the
high-frequency `safety factor'. The broadening of the action potential recovered
immediately during ischaemic conditions at 100Hz following 2400 stimuli but did not
recover following prolonged activity at 20Hz until circulation was restored, whereas
CMAP amplitude recovered immediately at both frequencies, suggesting that slowing of
conduction velocity may be dependent on metabolic factors at low stimulation
frequencies which in turn may depend on the contractile history of the muscle. Patients
with myophosphorylase deficiency (and thus unable to utilize glycogen), were studied to
investigate the importance of energy supply. A failure of ischaemic recovery of the
CMAP amplitude and no broadening of the CMAP after stimulated activity at 20Hz was
observed, suggesting a failure of excitation of individual muscle cells occurs resulting in
force failure in these individuals.
Reversing the pattern of stimulation resulted in an initial enhancement of low frequency
(10Hz) force and a prolonged maintenance of this force throughout the period
of contraction studied. This was independent of slowing of relaxation or excitation. The
initial force enhancement may result from the increased slowing of relaxation, and in
addition, a form of post-tetanic twitch potentiation operates to counteract the decline in
force despite a loss in excitation.
In conclusion, during stimulated contractile activity of the adductor pollicis,
mechanisms act to maintain or increase force generated per action potential distal to the sarcolemmal membrane, at both high and low frequencies of stimulation, thereby
counteracting mechanisms that lead to fatigue. It is postulated that the alterations in
intramuscular processes may allow voluntary isometrically contracting muscle to
optimize force production at the onset of a contraction where high motor unit discharge
rates are initially developed, delaying or eliminating the influence of excitation failure
which would lead to contractile failure once maximal force is achieved, and subsequently
to optimize contractile activation in the light of possible excitation failure as motor unit
discharge rates decline.
These findings may have important functional implications and may form the
basis of physiological strategies for optimizing force production in the development of
stimulation regimes for `functional electrical stimulation' or to any area of skeletal muscle
research in which fatigue resistance is of importance.