Large delayed plasma creatine kinase changes after stepping exercise

Muscle changes have been examined in 16 normal subjects (eight female) after both a 20-minute and a prolonged step test. Stepping differs from most exercise tests in that it involves eccentric contractions (negative work) in which the active muscle is lengthened. Plasma creatine kinase (CK), muscle force, contractile properties, and tenderness in the quadriceps were measured for up to 9 days after the exercise. Muscle tenderness was experienced only in the muscles that had performed eccentric contractions (i.e., stepped down). All subjects showed some early rise in CK (less than 400 IU/liter) but eight (both male and female) showed a much greater response (up to 34,500 IU/liter) which took a long time to reach peak levels (4-5 days after stepping). It is suggested that eccentric contractions involved in this form of exercise result in some particular form of muscle damage which, in susceptible subjects, may initiate changes giving rise to a large delayed release of muscle enzymes.     

Post-exercise depression of motor evoked potentials as a function of exercise duration

Post-exercise facilitation and post-exercise depression are phenomena described in motor evoked potentials (MEPs) elicited to transcranial magnetic stimulation. Brief, non-fatiguing muscle activation produces post-exercise facilitation, and prolonged fatiguing muscle activation produces post-exercise depression. We studied 12 normal subjects to determine whether post-exercise depression occurs before fatigue is reached. We recorded MEPs from the resting extensor carpi radialis muscle after increasing the duration of isometric wrist extension, at 50% of maximum voluntary contraction, until the muscle fatigued. Fatigue was defined as the inability to maintain that force. The mean exercise duration before the muscle fatigued was 130 s, and post-exercise depression occurred only beyond 90 s of exercise. We conclude that post-exercise depression is detectable only after prolonged muscle activation.     

Effect of exercise on the motor unit

The motoneuron part of this review deals with the changes in recruitment and firing rates of the motor unit types upon changes from a physically inactive life to endurance or strength training. The muscle fibers react to prolonged exercise by adaptation to a higher level of performance. A matter of discussion is the prerequisites for a transformation between the basic muscle fiber types, slow twitch and fast twitch, during voluntary (transsynaptic) activity, which is demonstrated after artificial nerve stimulation. The review includes current knowledge of muscle fiber transformation as an adaptive response to increased usage either by electrical stimulation or by transsynaptic neuronal activity. The metabolic adaptation related to increased endurance is reviewed with special reference to effects on muscle fibers. The increase in strength as a result of high resistance training is mainly the result of increased muscle cross-section. Whether this is solely the result of an increase in size of individual fibers or an increased fiber number is a controversial matter.     

The Effect of Fatigue on the Timing of Electrical Stimulation‐Evoked Muscle Contractions in People with Spinal Cord Injury

This study investigated the activation dynamics of electrical stimulation‐evoked muscle contractions performed by individuals with spinal cord injury (SCI). The purpose was to determine whether electrical stimulation (ES) firing patterns during cycling exercise should be altered in response to fatigue‐induced changes in the time taken for force to rise and fall with ES. Seven individuals with SCI performed isometric contractions and pedaled a motorized cycle ergometer with stimulation applied to the quadriceps muscles. Both exercise conditions were performed for five minutes while the patterns of torque production were recorded. ES‐evoked knee extension torque fell by 75% under isometric conditions, and the rate of force rise and decline decreased in proportion to torque (r = 0.91, r = 0.94, respectively). There was no change in the time for torque to rise to 50% of maximum levels. The time for torque to decline did increase slightly, but only during the first minute of exercise. Cycling power output fell approximately 50% during the five minutes of exercise, however, there was no change in the time taken for torque to rise or fall. The magnitude of ES‐evoked muscle torques decline substantially with fatigue, however, the overall pattern of torque production remained relatively unchanged. These results suggest there is no need to alter stimulation firing patterns to accommodate fatigue during ES‐evoked exercise.     

Mechano-sensitivity of normal and long term denervated soleus muscle of the rat

INTRODUCTION AND OBJECTIVES: Evidence showed that physical forces, as passive stretching or active contraction, may counteract various kinds of skeletal muscle atrophy due, for instance, to muscle immobilization, pathophysiology or denervation. Accordingly, active muscle contraction induced by functional electric stimulation is helpful to reduce the muscle atrophic state in denervated man. Moreover, there is evidence that also passive mechanical stimulation of the sarcolemnic membrane may reduce the atrophic muscle state. As to the mechanisms by which mechanical stimulation modulates muscle physiology and pathophysiology, there is a growing list of facts that signaling pathway to the nucleus involves stretch activated channels (SACs) of the sarcolemma and the cytoskeleton. SACs activation allowed a Ca(2+) inflow that activates Ca(2+)-dependent molecular signals. Cytoskeleton may be activated by Ca(2+)-dependent and -independent paths and its contraction and elongation represent not only a mechanical signal to the nucleus but also a stimulus for many molecular signals. The aim of this work was to evaluate in soleus muscle of the rat, the mechano-sensitivity of SACs before and after medium and long term denervation. METHODS: Electrophysiologic experiments were made in normal and denervated Soleus muscle of Wistar rats. Currents were recorded in voltage clamp by intracellular microelectrodes inserted in a single fiber. RESULTS: Our findings demonstrated that SACs were expressed in normal soleus muscle and that SAC currents were potentiated by muscle stretching. Another important result was that the sensitivity to stretching increased after denervation and was particularly evident in long term denervated muscles. DISCUSSION: The reported effects are in agreement with the effects of exercise on inducing muscle hypertrophy or with the positive effects on repairing the atrophic state of skeletal muscles by mechanical stimulation or, in denervated humans, by the functional electrical stimulation (FES).     

In vivo determination of altered hemoglobin saturation in dogs with M-type phosphofructokinase deficiency.

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myopathy and chronic hemolysis in affected humans and dogs, the only animal model available. Deficient individuals have impaired glycolytic metabolism, impaired oxidative metabolism, and increased hemoglobin-oxygen (HbO2) affinity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpose of this study was to determine if PFK-deficient muscle has abnormal oxygen saturation during exercise. Oxygen saturation of hemoglobin/myoglobin was measured noninvasively in skeletal muscle during progressive muscle activation using near-infrared spectroscopy (NIRS). Muscle metabolites were also measured using magnetic resonance spectroscopy (MRS). PFK-deficient and normal dogs were anesthetized and the cranial tibial muscles stimulated for 6 min at each of four different rates (1, 2, 4, and 8 Hz). With increasing stimulation, muscles from normal dogs showed progressive decrease in hemoglobin saturation. In contrast, PFK-deficient dogs exhibited either an increase in hemoglobin saturation or an initial decrease with no further change. PFK-deficient muscles accumulated 11.1 +/- 3.5 mmol/L of sugar phosphate which was not seen in normal muscle and had higher calculated [ADP] levels at each stimulation level, indicating impaired oxidative metabolism. These findings are consistent with the hypothesis that these animals have impaired oxidative metabolism and impaired muscle O2 extraction from hemoglobin due to increased HbO2 affinity. NIRS appears to be a useful noninvasive method of monitoring tissue oxygen saturation in normal or disease conditions.     

M-wave changes after high- and low-frequency electrically induced fatigue in different muscles

The mechanisms of fatigue-induced changes in evoked compound muscle action potential (M-waves) are not well documented. In rats, isolated fast-glycolytic (tibialis anterior, or TA) and slow-oxidative muscles (soleus, or SOL) were stimulated repetitively at a low (10-Hz) or high (80-Hz) rate. Decreased amplitude and prolonged duration of M-waves were only significant after high-frequency fatigue in TA and SOL muscles; that is, in the conditions in which an influx of calcium was measured. On the other hand, maximal force failure and maximal lactic acid increase in the bath medium occurred in TA muscle after high- and low-frequency fatigue trials. Postfatigue increase in potassium concentration occurred in all circumstances. Thus, M-wave alterations depend mainly on the stimulation paradigm and not on the muscle type, and cannot be used as a marker of changes in intracellular potassium or lactate ions. This amplifies understanding of the significance of M-wave changes in human exercise protocols.     

Absence of facilitation or depression of motor evoked potentials after contralateral homologous muscle activation

We have previously described post-exercise facilitation and post-exercise depression of motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS). To determine the presence of post-exercise facilitation after exercise of a contralateral muscle, MEPs were recorded from the resting right extensor carpi radialis (ECR) muscle while the left ECR muscle was activated, then immediately after brief left ECR activation, and, finally, immediately after brief right ECR activation. We repeated the experiment using the first dorsal interosseous (FDI) muscle. To determine the presence of post-exercise depression after exercise of a contralateral muscle, MEPs were recorded from the right ECR after prolonged exercise of the left ECR, followed by right ECR recording after its fatigue. The mean MEP amplitudes from the right ECR and the right FDI after brief activation were 187% and 266% of their pre-exercise values, respectively. There were no significant changes in MEPs recorded from the right ECR or FDI muscles during or immediately after brief activation of their left counterparts. The mean amplitude of MEPs recorded from the right ECR after it fatigued was approximately half the pre-exercise value, but there was no significant change in MEPs recorded from the right ECR after prolonged exercise of the left ECR. Therefore, neither post-exercise facilitation nor post-exercise depression occurred after contralateral homologous muscle exercise.     

Critical illness neuromuscular syndromes

Critical illness neuromyopathy (CINM) is suggested by bilateral diffuse weakness predominant in the proximal part of the limbs after improvement of the acute phase of critical illness. Although muscle and peripheral nerve are often involved in combination, muscle involvement alone is increasingly identified on electrophysiologic investigation, including direct muscle stimulation. CINM frequently involves the respiratory muscles and may result in delayed weaning and prolonged mechanical ventilation. Besides muscle immobilization and prolonged sepsis-induced multiorgan failure, which are risk factors for CINM, hyperglycemia and use of corticosteroids might have a deleterious effect on the neuromuscular system in critically ill patients, suggesting opportunities for preventive interventions.     

Effects of changes in pH on the afferent impulse activity of isolated cat muscle spindles

Muscle spindle activity has been shown to decrease in the sustained contracting muscle. The effect has been assumed to result from a declining fusimotor drive. Since accumulation of metabolites including H(+), lactate and CO(2) might also affect the receptor in the fatiguing muscle, the impulse activity of muscle spindles isolated from the cat tenuissimus muscle was characterized under varying degrees of extracellular pH, thus excluding any effect on fusimotor activity, blood supply and extrafusal muscle fibers. The isolated receptor was exposed to bathing fluids of pH 6.4, 7.4 and 8.4, and afferent discharge activity was recorded from the spindle nerve. Both primary and secondary endings responded similarly to changes in pH. Resting discharge frequency usually decreased with decreasing pH and increased with increasing pH. A sudden break-off in activity was observed with about 40% of primary endings and about 30% of secondary endings at pH 6.4. Experiments with slow stretch stimulation indicated that this effect was caused by a rising threshold of firing at the encoder site of the endings. With brief ramp-and-hold stretches, we tested the effects of changes in pH on the dynamic and static sensitivity of primary and secondary endings. When pH was reduced from 7.4 to 6.4, the initial burst activity at the beginning of the ramp phase increased in primary and secondary endings and the dynamic response increased in secondary endings, demonstrating that the dynamic properties of muscle spindle endings were usually augmented in the acidic milieu. The static properties rose as well because the static index of both types of ending increased significantly. By contrast, dynamic and static properties of both primary and secondary endings decreased significantly, when pH was increased from 7.4 to 8.4. The amplitude of tension that was measured during the passive stretch stimuli very slightly decreased in the acidic solution and very slightly increased in the alkaline solution. The decrease in the resting discharge activity at low pH supports those previous observations, which demonstrate a reduced peripheral input from muscle spindle afferents to the spinal motor nuclei during fatigue in the isometric contracting muscle. The present finding indicates that an attenuated afferent discharge is not only caused by a decreasing central activation of gamma-motorneurons, but may additionally be supported by a direct effect of protons on the muscle receptor itself. The accompanying augmentation of stretch sensitivity is suggested to correspond to the well-known increase in physiological tremor during exhaustive exercise.     

Effects of chronic low frequency electrical stimulation on normal human tibialis anterior muscle.

The loss of force that occurred during intermittent electrically evoked tetanic contractions was determined for the tibialis anterior muscle of normal subjects. Adult muscles showed a characteristic reduction of tension over the first two to three minutes until a steady plateau was reached. Muscles of young children showed no comparable decrease of the initial tension in response to this method of fatigue testing. After fatigue the muscles of both groups of subjects produced a higher proportion of tension at lower rates of stimulation. Following prolonged chronic low frequency stimulation at 8-10 Hz, adult muscles showed a significant increase (p less than 0.01) in fatigue resistance compared to unstimulated control: the muscles of the normal child showed no measured change. It is concluded that it is possible to alter the properties of adult human muscle by superimposed low frequency electrical stimulation.     

Evidence for subnucleus interpolaris in craniofacial muscle pain mechanisms demonstrated by intramuscular injections with hypertonic saline

The subnucleus interpolaris (Vi) has been identified as a major recipient for trigeminal ganglionic input from jaw muscles, and contains neurons with nociceptive properties similar to those in the subnucleus caudalis (Vc). Therefore, Vi may be another important site for processing craniofacial muscle nociception. The aims of present study were to define functional properties of Vi neurons that receive input from masseter muscle afferents by characterizing their responses to electrical, mechanical, and to chemical stimulation of the muscle. Ninety cells were identified as masseter muscle units in 11 adult cats. Most of these units (79%) received additional inputs from orofacial skin. Following the intramuscular injection of 5% hypertonic saline, 49% of the cells showed a significant modulation of either the resting discharge and/or responses to innocuous mechanical stimulation on their cutaneous receptive fields (RFs). The most common response to saline injection was an induction or facilitation of resting discharge which declined as an exponential decay function, returning to pre-injection level within 3-4 min. Forty-five percent of the muscle units that were tested with mechanical stimulation (13/29) showed a prolonged inhibition of mechanically-evoked responses. In most cases (8/13), the inhibitory response was accompanied by initial facilitation. The observations that Vi contained a population of neurons that receive small diameter muscle afferent inputs, responded to noxious mechanical stimulation on the muscle and to a chemical irritant that is known to produce pain in humans provide compelling evidence for the involvement of Vi in craniofacial muscle pain mechanisms.     

Mechanism of Botulinum Toxin in the Relief of Chronic Pain

For many years, the use of botulinum toxin in the management of dystonia and associated conditions, has been recognized as not only having a beneficial effect on muscle tone and activity, but also to be associated with significant and prolonged pain relief. It is difficult to understand how this effect could be mediated solely on the basis of the toxin's well-known property of chemodenervation of motor end plates. A second mode of action is demonstrated, in which effects on the muscle spindle play a prominent role, and which may enhance analgesia. A hypothesis is presented that a toxin degradation product may provide pain relief by mechanisms yet to be elucidated.     

Responses of inspiratory neurons of the dorsal respiratory group to stimulation of expiratory muscle and vagal afferents

In decerebrate, paralyzed and ventilated cats, we monitored the intracellular responses of 30 inspiratory neurons of the dorsal respiratory group (DRG) to stimulation of vagal and expiratory muscle (internal intercostal and abdominal) afferents. We hypothesized that the inhibitory effects of stimulation of expiratory muscle afferents, previously reported, would block the excitatory responses of inspiratory neurons of the DRG to vagal stimulation. Although prolonged stimulus trains to expiratory muscle afferents caused respiratory phase-switching, single shocks or short trains elicited no responses in 17 bulbospinal neurons, excitatory responses in 6, and inhibitory responses in 2. Of the 4 propriobulbar neurons tested, 2 had inhibitory responses and 2 did not respond. In only 2 neurons, both bulbospinal, did conditioning stimuli to expiratory muscle afferents block or reduce the excitatory effects of vagal stimulation. These results suggest that interaction of vagal and expiratory muscle afferents, which might account for the absence of a change in inspiratory duration despite increased vagal afferent feedback at elevated end-expiratory lung volumes, does not occur within the DRG.     

Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy.

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.     

Facilitation and reciprocal inhibition by imagining thumb abduction.

It is well known that motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of the motor cortex are facilitated by voluntary muscle contraction. We evaluated the effects of imagination of movements on MEP latencies of agonist and antagonist muscles in the hand using TMS. Twenty-two healthy volunteers were studied. TMS delivered at rest and while imagining tonic abduction of the right thumb. MEPs were recorded in response to magnetic stimulation over the scalp and cervical spine (C7-T1), and central motor conduction times (CMCT) were calculated. MEPs were recorded from right abductor pollicis brevis muscle (APB) and adductor pollicis muscle (AP) simultaneously. Imagination of abduction resulted in a shortened latency of MEPs in the APB muscle, and a prolonged latency in the AP muscle. But the imagination caused no significant change in the latency of MEPs elicited by stimulation over the cervical spine. The changes of the CMCT may account for these latency changes with imagination of movement. These findings indicate that imagination of thumb abduction facilitates motoneurons of agonist muscle and has an inhibitory effect on those of antagonist muscle (reciprocal inhibition).     

Mechanical properties of human ankle extensors after muscle potentiation.

The contractile properties of a muscle depend on the activation history of its motor units. At the same time as fatigue seems to impair muscle excitation-contraction coupling, post-tetanic potentiation can augment force production. The effects of post-tetanic potentiation on the mechanical muscle properties of the intact human ankle extensor muscles were investigated by a 4 degree dorsiflexion of the ankle joint during a sustained contraction. The contraction was elicited by 10 Hz electrical stimulation of the tibial nerve. The changes in the contraction torque and in the intrinsic muscle stiffness of the ankle extensors before and after prolonged electrically elicited muscle activation were measured. From the onset of continuous synchronized 10 Hz stimulation to the attainment of maximal torque, the ankle joint torque increased by 47%. At matched background contraction, the prolonged electrically elicited contraction increased the intrinsic muscle stiffness by 49%. The first stretch after prolonged stimulation gave rise to a 17% yield in the background contraction and a 73% yield in the torque increment. The findings imply that with fatigue an increase in the intrinsic stiffness of the pre-stretched muscle might operate as a "safety factor" to compensate for a reduced reflex-induced stiffness, keeping the total muscle resistance at a high level in the active muscle.     

Effects of temperature on neuromuscular electrophysiology.

Like nearly all biologic structures, the peripheral nervous system is remarkably temperature sensitive. Clinical neurophysiologists are most aware of the untoward effects of cooling on nerve conduction studies, including reduced conduction velocity, prolonged distal latency, and increased response amplitude and duration. However, familiarity with the effects of temperature variation on the peripheral nervous system can also provide a deeper understanding of the physiological mechanisms underlying the function of nerve, muscle, and neuromuscular junction in health and disease. Intentional temperature alteration can also improve the diagnostic accuracy of certain electrophysiologic tests, such as the use of heat when performing repetitive nerve stimulation in myasthenia gravis or the use of cold during needle electromyography in some of the myotonic disorders. Finally, extremes of temperature have long been known to produce permanent neuronal dysfunction; recent investigations are beginning to elucidate the mechanisms of such injury.