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Biomedical subjects

A J McComas

Publications and source records attributed to A J McComas.

At least 19 recordsLinked to original sources

Motor unit estimation: anxieties and achievements.

The history of motor unit number estimation (MUNE) is given, together with brief descriptions of the various methods presently available. A small muscle of the hand contains about 100 motor units and greater numbers are found in larger muscles; beyond 60 years the numbers begin to decline. In ALS approximately half the motor units cease to function within 6 months of the involvement of the motoneuron pool, while in adult spinal muscular atrophy further loss may not occur over several years. The reduction in MUNE values in myotonic dystrophy remains an enigma, but even more curious are the losses and subsequent recoveries occasionally observed in hyperthyroidism and chronic renal failure; possibly, nontransmitting ("silent") synapses are involved. MUNE may also be used to study CNS problems such as hemiplegia and congenital brachial palsy. The availability of more powerful computers for EMG should lead to advances in MUNE.

Adult

Pseudofacilitation: a misleading term.

The possible causes of the transient enlargement of muscle compound action potentials during repetitive stimulation ("pseudofacilitation") are considered. The phenomenon cannot be due to mechanical artefact, while hypersynchronization of the muscle fiber action potentials, the usual explanation, can only make a minor contribution. A more convincing explanation, for which there is now experimental evidence, is that the muscle fibers undergo hyperpolarization, due to the intramuscular release of norepinephrine and consequent stimulation of the electrogenic Na+,K(+)-pump. Defective phosphorylation of the Na+,K(+)-pump is a possible cause of the transient weakness and myotonia in myotonic dystrophy.

Action Potentials

Effect of selective and nonselective beta-blockade on skeletal muscle excitability and fatiguability.

The effects of beta-blockade on skeletal muscle excitability and fatiguability during exercise were examined. Ten healthy males (mean age 21.9 +/- 1.1 yr) performed a 4-min fatigue protocol consisting of intermittent isometric voluntary contractions of the knee extensors in one leg. Subjects performed the exercise after treatment with placebo, 100 mg metoprolol, or an equipotent dose of propranolol (60 mg, n = 1; 80 mg, n = 8; 100 mg, n = 1) twice a day for 76 h before testing according to a randomized double-blind design. The evoked twitch torque, maximal voluntary torque, and maximal M-wave amplitude were unaffected by the beta-blockade treatments before fatigue. During the placebo trial, there were significant reductions in the evoked and voluntary torques (77 +/- 15 and 55 +/- 11%, respectively) after the fatigue protocol; however, both the voluntary electromyogram and evoked M waves were well maintained throughout fatigue. The beta-blockade treatments had no significant effect on torque or electromyogram activity over the course of the exercise. Thus, despite evidence for an impairment of dynamic exercise performance with beta 1- and beta 1,2-blockade, there appears to be no effect of these agents on muscle excitability and fatiguability during isometric muscle activity.

Adrenergic beta-1 Receptor Antagonists

Human neuromuscular adaptations that accompany changes in activity.

Neuromuscular adaptations probably occur at all levels of the motor pathway, following changes in muscular activity. Adaptations have been mostly investigated in muscle fibers after heavy-resistance and endurance training. In strength training the rapid improvement is due to poorly understood neural factors, with muscle fiber hypertrophy occurring rather later; fiber hyperplasia is probably unimportant. In contrast to other mammals, muscle fibers in humans do not readily change from "slow" to "fast" and vice versa, although there may be a period of plasticity in infancy especially responsive to weightbearing. A proportion of the changes in the fibers, following training, is probably brought about by stretch-activated mechanisms, in which second messengers express immediate early genes and the latter, in turn, promote the transcription of "muscle" genes; other cellular adaptations occur at the level of mRNA translation. In the spinal cord, adaptations following hemiparesis include a loss of functioning motor units. Impaired motor drive occurs not only in organic brain lesions but also after periods of disuse. In persons with amputations, the peripheral nerve stump undergoes degenerative changes; somatosensory cortical evoked responses, following stimulation of the stump, are diminished. It is possible that both sensory and motor cortical representations are increased for neighboring regions of the body.

Adaptation, Physiological

Motor unit populations in healthy and diseased muscles.

The numbers of functioning motor units can be estimated in proximal and distal muscles of human limbs by an electrophysiological technique in which the mean sizes of the motor unit potentials are compared with the maximum M-waves of the same muscles. Although manual methods of estimation have been used successfully in the past, the introduction of automated techniques has brought considerable advantages, including greater objectivity and reduced contamination of the results by "alternation." In healthy subjects, the intrinsic muscles of the hand have approximately 100 motor units each, and the biceps brachii muscle has only slightly more. With advancing age, there is a loss of motor units, which appears to be more pronounced in distal muscles. The motor unit estimating methodology has been found to be of value in the diagnosis and assessment of patients suspected of having muscle denervation. In amyotrophic lateral sclerosis, the mean rate of motor unit loss is swift, whereas in late-onset cases of spinal muscular atrophy, the reduction in the motor unit population does not appear to progress. In only the most rapidly deteriorating cases of post-polio syndrome is it possible to demonstrate further loss of motor units. In all of these denervating disorders, and in peripheral neuropathies, the importance of collateral reinnervation as a compensatory mechanism is emphasized.

Adaptation, Physiological

Abnormal M-wave responses during exercise in myotonic muscular dystrophy: a Na(+)--K+ pump defect?

Maximum M-waves (muscle compound action potentials) were studied in the abductor pollicis brevis (APB), extensor digitorum brevis (EDB), and tibialis anterior (TA) muscles of 12 patients with myotonic muscular dystrophy (MMD) and in the same number of control subjects, matched for age and sex. The peak-to-peak amplitudes and voltage-time areas of the responses were measured at rest, between 40 maximum voluntary contractions (each lasting 3 s) and also during a 2-min recovery period. In 34 of the 36 control muscles the M-waves potentiated during the period of intermittent voluntary contractions. In the MMD patients, however, the M waves exhibited initial declines in 25 of 30 muscles. In the APB and EDB muscles the normalized mean values for the smallest M-waves, recorded during the 350 s total observation periods, differed significantly between the 2 groups of subjects. It is suggested that the sarcolemmal Na(+)-K+ pump has a raised threshold for activation in MMD patients.

Adult

Invited review: motor unit estimation: methods, results, and present status.

The renewed interest in motor unit estimation (counting) has coincided with the introduction of computer-based methodology and with the application of the technique to proximal as well as distal muscles. The advantages and disadvantages of the different methods are considered, together with the assumptions inherent in this type of examination. In normal subjects, the extensor digitorum brevis (EDB) muscle has approximately 200 motor units while each of the intrinsic muscles of the hand has about 100 units; larger muscles in the limbs contain greater numbers of units. Beyond the age of 60 years, there is a decline in the number of functioning motor units in both proximal and distal muscles. In denervating disorders, motor unit estimation is useful for diagnosis and assessment; abnormal values may often be observed in muscles judged clinically to be unaffected. Serial studies have enabled the rate of motor unit loss to be determined in ALS and in spinal muscular atrophy. Depletion of motor units has also been found following upper motoneuron lesions caused by injury to the spinal cord or by cerebral hemorrhage; trans-synaptic dysfunction has been presumed responsible. Rather surprisingly, reduced numbers of motor units have been observed in a variety of myopathic disorders; of these, the most consistent abnormalities have been reported in myotonic muscular dystrophy.

Computers

The numbers and relative sizes of motor units estimated by computer.

A fully automated system is described for estimating the numbers and relative sizes of functioning motor units in proximal and distal muscles of the arm and leg. In this system, a computer controls the motor nerve stimulation, and analyzes the potentials evoked from the muscles; a subprogram searches for instances of "alternation." In 33 healthy volunteers, aged 21 to 56 years, the median-innervated thenar muscles of one hand were tested 2 to 3 times; the mean motor unit estimate was 228 +/- 93 SD. For similar numbers of biceps brachii, extensor digitorum brevis, and vastus medialis muscles, the respective mean values were 113 +/- 40, 131 +/- 45, and 229 +/- 108 units. The reproducibility of the method was such that the overall coefficient of variation, for the normalized results from the 121 muscles studied, was 22%. The reliability of the automated method was doubled if 3 estimates, rather than one, were performed on each muscle. Comparisons of the results obtained by automated and "manual" methods indicated that the computer-derived values tended to be lower by approximately 33%.

Action Potentials

Reflex inhibition of human soleus muscle during fatigue.

1. Human soleus muscles were fatigued under ischaemic conditions by intermittent stimulation at 15 Hz. When maximal voluntary plantarflexion was then attempted, the loss of torque was found to be associated with a reduction in voluntary EMG activity. 2. The decrease in EMG activity could not have been due to 'exhaustion' of descending motor drive in the central nervous system since fatigue had been induced by electrical stimulation of peripheral nerve fibres. Similarly, the decrease could not be explained by changes at the neuromuscular junction or muscle fibre membrane, since changes in the M wave (evoked muscle compound action potential) were relatively modest. 3. When the excitability of the soleus motoneurones was tested during fatigue, using the H (Hoffmann) reflex, it was found to be significantly reduced. Control experiments with ischaemia or electrical stimulation, but without fatigue, failed to demonstrate any significant effects on reflex excitability. 4. The findings in this study favour the concept of reflex inhibition of alpha-motoneurones during fatigue.

Action Potentials

Operation Everest II: neuromuscular performance under conditions of extreme simulated altitude.

The force output of the ankle dorsiflexors was studied during a 40-day simulated ascent of Mt. Everest in a hypobaric chamber; both electrically activated and maximal voluntary contractions (MVCs) were employed. The purpose of this study was to establish whether, under conditions of progressive chronic hypoxia, there was a decrease in muscle force output and/or increased fatigability. We also attempted to identify the main site of any failure, i.e., central nervous system, neuromuscular junction, or muscle fiber. Muscle twitch torque (Pt), tetanic torque (Po), MVC torque, and evoked muscle compound action potential (M wave) were monitored during 205-s exercise periods in five subjects at three simulated altitudes (760, 335, and 282 Torr). All three types of torque measurement were well preserved at the three altitudes. In some subjects, the responses to stimuli interpolated during repeated MVCs provided evidence of "central" fatigue at altitude. In addition, the rate of fatigue during 20-Hz electrical stimulation was greater (P less than 0.01) at altitude and there was increased fatigability of the twitch (P less than 0.025); however, the M wave amplitude was maintained. We conclude that central motor drive becomes more precarious at altitude and is associated with increased muscle fatigue at low excitation frequencies; the latter is the result, in part, of chronic hypoxia and occurs in the muscle fiber interior because no impairment in neuromuscular transmission could be demonstrated.

Adult

Contractile properties of human skeletal muscle in childhood and adolescence.

Using a combination of single maximal stimuli and maximum voluntary contractions, a comparison has been made of muscle properties in pre- and post-pubertal male subjects. In the dorsiflexor and plantarflexor muscles of the ankle, the twitch and maximum voluntary torques were approximately twice as large in the older subjects; the mean height and mean weight increased by factors of 1.20 and 1.86 respectively. The only other muscle parameter that changed, as a function of age, was the contraction time of the ankle dorsiflexors; the mean value was significantly longer in the older subjects. In the younger subjects, there were already clear differences between the dorsiflexor and plantarflexor muscles, the former developing smaller torques and having shorter contraction and half-relaxation times, greater post-activation potentiation and more susceptibility to fatigue. Even in the youngest subject, motor unit activation was complete in the ankle dorsiflexors; although this was not always true of the plantarflexors, the difference between the two subject groups was not significant.

Adolescent

Prolongation of twitch potentiating mechanism throughout muscle fatigue and recovery.

Measurements have been made of twitch amplitudes in human ankle dorsiflexor muscles during and following fatiguing electrical stimulation. In six subjects, studied with the arterial circulation occluded, the twitch was observed to undergo an early potentiation (mean, 99 +/- 50%) followed by complete disappearance. A second, smaller phase of potentiation (mean, 25 +/- 30%) occurred during recovery and gave way to prolonged depression of the twitch. A comparison of these results with those obtained with an intact circulation suggested that the four phases in the behavior of the twitch were the net result of two processes, potentiation and fatigue, with different time courses. Provided they are timed appropriately, observations of twitch amplitude can provide useful information concerning the development of, and recovery from, muscle fatigue.

Adult

Increased sodium pump activity following repetitive stimulation of rat soleus muscles.

1. Soleus muscles of anaesthetized rats were stimulated tetanically (4 s at 20 Hz every 5 s for 5 min), following which the resting and action potentials were measured in surface fibres. 2. At the end of the stimulation period, the mean resting potential was found to have increased from a control value of -79.5 +/- 4.8 mV (mean +/- S.D.) to -90.5 +/- 6.3 mV. The hyperpolarization started to decline after 9 min but was still present at 15 min. 3. Associated with the membrane hyperpolarization was an increase in the mean amplitude of the muscle fibre action potential, from 82.2 +/- 10.8 to 96.8 +/- 10.0 mV. 4. Both the hyperpolarization and the enlargement of the muscle fibre action potential were abolished by 1.25 X 10(-4) M-ouabain, cooling the bathing fluid to 19 degrees C or removing K+ from the bathing fluid. 5. The results are explained in terms of an increase in electrogenic sodium pump activity resulting from tetanic stimulation. When the bathing fluid contained 20 mM-K+, the mean resting potential of stimulated fibres was approximately -30 mV greater than that calculated from the Goldman-Hodgkin-Katz equation. 6. The increase in sodium pumping not only acts to restore the concentrations of Na+ and K+ on either side of the muscle fibre membrane, but, through its electrogenic effect, enables fibres to remain excitable during continuous contractile activity.

Action Potentials

M wave potentiation during and after muscle activity.

The M wave (muscle compound action potential) has been shown to enlarge between successive 3-s voluntary contractions of the human thenar and extensor digitorum brevis (EDB) muscles. The changes, which affected both the amplitude and the area of the M wave, were more obvious in the thenar than in the EDB muscles. In the thenar muscles the mean amplitude was already significantly enlarged after the first voluntary contraction and close to the maximal value by the third (mean maximal increase 23.6 +/- 12.6% of control). The increase in mean M wave area was more gradual, reaching a maximum of 29.3 +/- 14.1% at 100 s. After the voluntary thenar contractions ceased, the amplitude of the M wave subsided more rapidly than the area and had regained the control value within 50 s. The magnitude and time course of the increase in EDB M wave area (maximum change 25.9 +/- 15.2%) were similar to those of the thenar muscles; however, the subsequent decline was slower. The amplitude of the EDB M wave showed the least change, and the maximum increase (11.4 +/- 9.6%) occurred early in the postcontraction period. In both muscles the changes in M wave amplitude and area were significantly different from the control values.

Action Potentials

Longitudinal structure and innervation of two mammalian hindlimb muscles.

The possibility of a topographic relationship between the spinal cord and the longitudinal axis of a muscle has been explored in two mammalian hamstring muscles: the rat semitendinosus (ST) and biceps femoris (BF). In both muscles the fibers did not extend the full length of the respective muscle bellies but were arranged in longitudinal arrays. There were two such arrays in BF and three in ST; monopolar recordings revealed that each array had a transverse band of endplates extending across the middle part. By stimulating ventral nerve roots in the lumbosacral outflow, it was found that L5 made the greatest contribution to the innervation of both ST and BF, with lesser inputs coming from adjacent roots. In neither ST or BF was there any evidence of a topographic relationship between the spinal cord and the muscle belly.

Animals

Reduced voluntary electromyographic activity after fatiguing stimulation of human muscle.

1. After ischaemic ankle dorsiflexor muscles had been fatigued by repetitive stimulation of the peroneal nerve at 15 Hz, there was a reduction in voluntary EMG activity which persisted as long as the arterial cuff remained inflated. 2. The reduction in voluntary EMG activity could not have been due to loss of excitability at the neuromuscular junctions or muscle fibre membranes since the M-waves (muscle compound action potentials) evoked by peroneal nerve stimulation were well maintained. 3. The preceding observations were consistent with the view that the reduction in EMG activity was due to reflex inhibition of motoneurones by afferents from the fatigued muscle. 4. The absence of responses to stimuli interpolated among the voluntary activity indicated that any motor units which could not be recruited in the fatigued muscle were no longer capable of generating tension.

Action Potentials

Functional and structural adaptations in skeletal muscle of trained athletes.

Twitch contractile and ultrastructural characteristics of the human triceps surae were determined in six male strength-trained athletes, six endurance-trained athletes, six active controls, and seven sedentary controls of similar height and age. Twitch contraction time in the triceps surae complex was 20% longer in strength-trained and sedentary groups than in endurance-trained or active control groups. In the 15 subjects peak twitch torque and one-half relation time in the triceps surae were 22.6 +/- 7.9 N.m and 91.1 +/- 18.3 ms, respectively. Mean fiber area in the gastrocnemius was approximately 1.6-, 1.7-, and 2.5-fold greater in the active control, endurance-trained, and strength-trained groups, respectively, relative to the sedentary group. Despite these large differences in fiber areas, the fiber fractional volume of the sarcoplasmic reticulum-transverse tubule network averaged 3.38 +/- 0.86% and 5.50 +/- 0.94% in type I and type II fibers, respectively, in all subjects. The fractional fiber volume of cytoplasm and lipid were similar for all four groups. However, mitochondrial volume was approximately 30% lower in both fiber types of the strength-trained group relative to the other groups. This implies that with exercise-induced hypertrophy, the sarcoplasmic reticulum, cytoplasm, and lipid components increase proportionately with contractile protein, whereas the mitochondrial fraction does not. The proportion of type I fibers in the soleus, medial gastrocnemius, and lateral gastrocnemius was 75.2 +/- 8.3, 58.5 +/- 6.1, and 52.4 +/- 4.2%, respectively, and was similar in all subject groups. The results demonstrate that twitch duration is prolonged in strength-trained athletes relative to endurance athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent