Endplate dysfunction in healthy muscle following a period of disuse.

The objective of this study was to test the hypothesis that muscle disuse can result in abnormal neuromuscular transmission. Six healthy volunteers (2 females, mean age = 33 years) participated in the study. Cast immobilization of one leg, for a period of 4 weeks, was used as a model of disuse; the contralateral leg was used as a control. Three testing sessions, consisting of stimulation single fiber electromyography of the soleus muscle bilaterally, were done before, immediately after, and 4 weeks after cast removal. The main outcome measure was neuromuscular jitter, measured as the mean of the consecutive differences (MCD) of single muscle fiber potentials. A mean MCD was calculated for each muscle, and the data from all subjects was pooled to calculate a sample mean MCD. The control side showed good reproducibility of results between testing sessions. The experimental side showed a significant increase of the sample mean MCD after casting when compared to: preimmobilization values (P < 0.001), and to the control side (P < 0.001). After 4 weeks of recovery, the sample mean MCD returned to preimmobilization values. This study presents evidence that muscle disuse, without any neuromuscular disease, can result in a reversible dysfunction of neuromuscular transmission.

Neuromuscular adaptations during 30 days of cast-immobilization and head-down bedrest.

Prolonged skeletal muscle disuse, during space flights and on Earth, produces distinct adaptive changes in the neuromuscular system of human subjects. There is a significant decline in muscle mass and strength, exercise capacity, fatigue resistance, integrated EMG (IEMG) output and time-dependent alterations in the behavior of Hoffman (H) and deep tendon reflexes. The objective of this study was to examine the changes in excitability of segmental motoneuronal network and its influence upon gastrocnemius-soleus (G-S) function in healthy male and female subjects, who underwent either 6 degrees head-down bedrest (HDB) or unilateral cast-immobilization (CIM) for a period of 30 days.

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats.

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

Postpoliomyelitis muscle weakness: a prospective study of quadriceps strength.

The objective of this study was to evaluate the presence of progressive postpoliomyelitis muscle weakness (PPMW) in affected individuals 20 to 40 years after the initial polio infection. Over a three-year period, the isometric and isokinetic strength of the quadriceps femoris muscle was studied in seven symptomatic patients with previous poliomyelitis (mean = 38.3 years from infection) to determine if quadriceps strength decreased during the three years. Each patient had a quadriceps affected by polio on one side and a clinically nonaffected quadriceps on the contralateral limb. The maximal isometric force and the peak isokinetic force of the affected quadriceps (AQ) and nonaffected quadriceps (NQ) muscles were tested on a computerized isokinetic dynamometer machine at six-month intervals. Isometric force increased significantly, by 29% per year (p less than .02) in the AQ and by 14% per year (p less than .05) in the NQ. Paired analysis to determine the change in strength between the affected and nonaffected muscles for the isometric data showed a mean nonsignificant increase in the AQ of 14% per year (p = .01). The change in peak isokinetic force demonstrated a significant increase in the AQ of 35% per year (p less than .05); whereas, the NQ peak isokinetic force increased 15% per year which was not statistically significant. Paired analysis to determine the change in strength between the affected and nonaffected muscles for the isokinetic data showed a nonsignificant relative increase in the AQ of 20% per year (p less than .06).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous electromyographic potentials in chronic spinal cord injured patients: relation to spasticity and length of nerve.

Nine patients with complete cervical spinal cord injury (SCI) had their vastus medialis, tibialis anterior, and gastrocnemius muscles evaluated with an electromyographic (EMG) examination in the acute (four to eight weeks) and chronic (more than one year) phases. The hypothesis that spontaneous EMG activity changes with time was assessed. During the chronic phase evaluation, a conduction study was performed to rule out peripheral nerve damage, and the amount of reflex activity was assessed on a scale of 0 to 5 (0 = areflexia; 5 = greater than 5 beats of clonus) to estimate the amount of spasticity. Subjects demonstrated normal conduction through the sensory (sural nerve) and/or motor segments of the peroneal and tibial nerves. In the acute phase, each muscle had spontaneous activity with no significant variation between different muscles of the same patient. In the chronic phase, there was a positive correlation between the degree of spontaneous activity in a muscle and the length of its axon (p less than .01) and a negative correlation between the amount of spontaneous activity and the degree of reflex activity (p less than .01). Specifically, the lower motor neuron in the chronic phase of an SCI seems to behave much like an axonopathy where the degree of spontaneous EMG activity is dependent on the length of the axon, with the additional concept that spontaneous activity is inhibited by spasticity.

Recovery of strength at the zone of injury in motor complete and motor incomplete cervical spinal cord injured patients.

This study compared the time of recovery at the zone of injury between motor complete (Frankel A and B) and motor incomplete (Frankel C and D) cervical spinal cord injured patients for the biceps (C5), extensor carpi radialis (C6), and triceps (C7) muscles. Manual muscle testing was performed initially three to seven days postinjury, then weekly for four weeks, and then monthly for six months. Subjects between the ages of 15 and 70 years with C4, C5, C6, or C7 neurologic levels were classified according to whether their selected muscle was greater than 0/5 and less than 3/5 grade (n = 32) or greater than or equal to 3/5 grade (n = 28) at initial evaluation. Subjects were further classified based on their Frankel score. Motor incomplete patients with muscle strength less than 3/5 had an average time of recovery to grade 3/5 of 0.9 months (median = 2 weeks), and all seven patients achieved grade 3/5 by two months postinjury. Motor complete patients had an average time of recovery to grade 3/5 of 1.8 months (median = 2 months), and 18 of 25 patients achieved grade 3/5 by two months postinjury (p = 0.1). For muscles greater than or equal to 3/5, motor incomplete subjects had an average time for improvement of one full grade of 1.5 months (median = 2 months), and motor complete subjects had an average time for improvement of one grade of 2.3 months (median = 1 month, p = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Deep vein thrombosis: prophylaxis in acute spinal cord injured patients.

The purpose of this prospective, randomized study was to evaluate the efficacy of low-dose heparin, alone or in combination with electric stimulation, in the prevention of deep vein thrombosis (DVT) in C2 to T11 motor complete and incomplete-preserved motor, nonfunctional spinal cord injured patients. The tibialis anterior and gastrocnemius-soleus muscle groups were stimulated bilaterally, using 50 microsecond pulses given at 10Hz with a four-second "on" and an eight-second "off" cycle for 23 hours daily over a 28-day period. Forty-eight patients, less than two weeks after injury, were randomly assigned to saline placebo (n = 17), low-dose heparin (5,000U, subcutaneous every eight hours) (n = 16), and low-dose heparin plus electric stimulation (n = 15). A normal 125-I fibrinogen scan and impedance plethysmography were required for entry into the study. Surveillance for DVT was evaluated by daily 125-I fibrinogen scanning. Venography was performed to confirm a positive impedance plethysmography and/or 125-I fibrinogen scanning tests for two consecutive days and at the completion of the study. The incidence of DVT was 8 of 17 in the placebo group, 8 of 16 in the low-dose heparin group, and 1 of 15 in the electric stimulation plus low-dose heparin group. The use of electric stimulation plus low-dose heparin significantly (p less than 0.05) decreased the incidence of DVT compared to the other treatments.

Overwork-induced axonal hypertrophy in the soleus nerve of the rat.

Effect of overwork, induced by synergistic tenotomy (bilateral tenotomy of the gastrocnemius and the plantaris muscles) of the soleus muscle, was evaluated on areas of the large myelinated axons (LMA) (greater than 19.5 micron 2), in the soleus nerve (the tibial nerve branch innervating the soleus muscle) of the rat. Three lots (n = 12-16) of young adult male (body weight of 275 to 325 g), Sprague-Dawley rats were used. One lot of 16 animals was kept as normal, while the other two underwent bilateral L4 or L5 spinal nerve sectioning. Six to seven animals each from the normal, L4-, and L5 neurectomized animals underwent bilateral synergistic tenotomy of the soleus so that the soleus was retained as the sole plantar-flexor of the ankle joint. The remaining animals were kept as normal or neurectomized control groups. Thus, the six groups studied were normal control (n = 9); normal synergistically tenotomized (n = 7); L4 neurectomized control (n = 8); L4 neurectomized and synergistically tenotomized (n = 6); L5 neurectomized control (n = 8); and L5 neurectomized and synergistically tenotomized (n = 7). Seven days after surgery, the soleus muscles were used to evaluate the muscle weights. The soleus nerves were evaluated for the number plus areas of the LMA by computerized planimetric procedures. The data revealed a 13.9% (p less than 0.05) increase in areas of the LMA in the L5 neurectomized control group; whereas the L5 neurectomized and synergistically tenotomized group showed a 39.6% (p less than 0.01) increase in areas of the LMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle atrophy in rheumatoid arthritis.

The purpose of this paper is to describe some research opportunities in the area of muscle atrophy secondary to arthritis. Future research should utilize quantitative methods of evaluating muscle atrophy such as computerized tomography or ultrasonography. The gross muscle atrophy should be further characterized by muscle fiber type measurements. These techniques as well as biochemical determinations should be utilized to identify mechanisms of muscle atrophy as well as determine ideal methods for reversing muscle atrophy and weakness.

Capillary fiber ratio and electrolyte content of compensatory hypertrophied rat soleus.

Capillary-to-fiber ratio and the content (mu moles/g muscle) of Na, K, Mg, Ca and Zn was measured in compensatory hypertrophied (CH) soleus muscles of adult Sprague-Dawley rats. The soleus hypertrophy was induced by unilateral tenotomy of the gastrocnemius and the plantaris muscles. Seven days after synergistic tenotomy the compensatory hypertrophied Soleus muscles showed no difference in the capillary-fiber ratio, Sr-extractable calcium ([Ca]Ext.) or the total content of Na, K, Mg and Zn. However, compared to the contralateral control side, the CH muscles showed an increase in the wet muscle weight (31.6%, P less than 0.01) and a significant decline (57.1%, P less than 0.05) in the residual calcium ([Ca]Res.) and 43.2% (P less than 0.05) decrease in the total calcium ([Ca]Total) content. It is concluded that during compensatory hypertrophy of skeletal muscles, the residual Ca reserves are significantly depleted, which may lead to a lower isometric tension generation in the muscle.

Muscle atrophy and histopathology of the soleus in 6-mercaptopurine-treated rats.

In this study, male and female Sprague-Dawley rats were treated neonatally with 6-MP-treatment (2 mg/kg s/c, between 2 and 22 days after birth) and evaluated at six months of age. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) muscle fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Effects of 6-mercaptopurine on developing muscle cells in vitro.

Treating differentiating muscle cells in vitro with 6-MP has resulted in a number of myopathic changes, some of which resemble the changes seen in 6-MP-treated neonatal rats. 6-MP treatment was cytotoxic to myotubes, but not myoblasts. The degenerative changes observed in 6-MP-treated myotubes were quite similar to those described in the neonatal rats by Alleva and his colleagues (1981). The results of this investigation demonstrate that differentiating muscle grown in vitro can be used to investigate tissue-specific toxicity, although the mechanism by which 6-MP results in selective toxicity in myotubes remains to be elucidated.

Overwork effect on partially denervated rat soleus muscle.

The purpose of this study was to assess the effect of overwork induced by synergistic tenotomy on the muscle weight (MW) and isometric tetanic tension (Po) of the partially denervated rat soleus muscle. Forty-nine young adult male Sprague-Dawley rats were divided into six groups (n = 5 to 9): normal control (N), normal synergistically tenotomized (N-ST), L4 denervated control (L4), L4 denervated synergistically tenotomized (L4-ST), L5 denervated control (L5), and L5 denervated synergistically tenotomized (L5-ST). Bilateral L4 or L5 root transections produced partial denervation. To yield soleus muscle overwork the gastrocnemius and plantaris muscles were bilaterally tenotomized in all ST groups at the time of denervation. The soleus MW and Po were examined seven days following denervation and tenotomy. Compared to their respective controls, there was increased MW in the N-ST (43.5%, p less than 0.01) and the L4-ST (38.6% p less than 0.01) groups. The L5-ST group showed no significant change in MW compared to the L5 group. Tetanic tension was increased only in the N-ST group. The L4-ST and L5-ST groups did not show any change in Po compared to their respective controls. Despite marked denervation, the L5 group did not show any atrophy as compared to the N group, suggesting passive stretch of the denervated muscle fibers, hypertrophy of the innervated muscle fibers and peripheral sprouting prevented the loss of MW due to denervation. Overwork in this markedly denervated group could not produce any increase in the MW or Po.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical stimulation of sciatic nerve of rats after partial denervation of soleus muscle.

The purpose of this study was to determine the effect of electrical stimulation of the sciatic nerve on the recovery of the weight and tension of partially denervated rat soleus muscle. Electrodes were implanted unilaterally adjacent to the sciatic nerve in 30 adult female Wistar rats. Fifteen rats underwent bilateral partial nerve section (PNS) of the sciatic nerve to stimulate the plantar flexors. Both the normal and partially nerve sectioned animals were stimulated unilaterally with 4 ms, 2-4 mA current given at 10 pulses per second. Groups of five normal and five partially denervated animals were stimulated for two, four or eight hours per day, five days per week for six weeks. The soleus muscles were evaluated for muscle weight (MW), twitch (Pt) and tetanic (Po) tension, contraction time (CT) and fiber areas of the type 1 and type 2 fibers. The MW, Pt, Po, CT and area of the type 1 and 2 muscle fibers of the normal soleus muscles were 114 +/- 15 mg, 21 +/- 4 mg, 95 +/- 20 mg, 95 +/- 21 ms, 1532 +/- 84 microns m2 and 1267 +/- 136 microns m2 respectively. The electrical stimulation had no effect on the normal soleus muscles. The MW, Pt, Po, CT and area of type 1 and 2 muscles fibers of the partially denervated control soleus muscles were 59 +/- 12 mg, 9 +/- 4 mg, 22 +/- 14 mg, 104 +/- 32 ms, 1028 +/- 514 microns m2, and 849 +/- 292 microns m2 respectively. Two hours of electrical stimulation significantly increased the MW (87 +/- 17 g), Pt (17 +/- 6g), and Po (49 +/- 23 g) but not the type 1 and 2 fiber areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle atrophy and histopathology of the soleus in 6-mercaptopurine-treated rats.

This study was conducted to examine the histochemical changes occurring due to neonatal 6-mercaptopurine (6-MP) treatment (2 mg/kg, sc, between 2 and 22 days after birth) in the slow-twitch muscle (soleus) of adult male and female rats. At 6 months of age, the control and the 6-MP-treated rats were evaluated for the sciatic nerve conduction to the soleus and for the soleus atrophy and histopathology of the type I (slow-twitch) and type II (fast-twitch) muscle fibers. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in fiber areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Recovery of reinnervating rat muscle after cast immobilization.

We evaluated the recovery of the reinnervating rat plantar flexor muscles after different periods of casting and then decasting the lower extremities. Four groups of 4-month-old, female Wistar rats underwent bilateral crush-denervation of the sciatic nerve at the sciatic notch. Two weeks after nerve crush, the hind legs of three groups of rats were immobilized with bilateral casts at the knee and ankle joints and the fourth group was a control group. Of the three casted groups, one was mobilized after 1 week and another group after 3 weeks of casting. The third experimental group remained casted until the end of 6 weeks. Six weeks after the nerve crush, all groups were evaluated for muscle weights of the soleus, plantaris, and gastrocnemius; absolute amounts of the myofibrillar, sarcoplasmic, and stromal proteins in the gastrocnemius; the fiber diameters and percent composition of type I and type II fibers in the soleus and plantaris; and the isometric contractile properties of the soleus muscle. Compared with the denervated control group, the experimental groups revealed the following: (i) Four weeks of casting caused a reduction in wet weight (range 30.6 to 40.4%, P less than 0.01) in the soleus, plantaris, and gastrocnemius muscles. Decasting led to an earlier recovery of the soleus than of the plantaris and gastrocnemius muscles. (ii) The myofibrillar protein returned to control values with 3 weeks of decasting but the stromal protein remained significantly elevated and the sarcoplasmic protein significantly depressed regardless of the period of mobilization. (iii) Except for the type I fibers in the plantaris, the remainder of the muscle fibers in the soleus and plantaris decreased in size due to casting. Only the type I muscle fibers of the soleus increased in size with longer periods of mobilization. (iv) Four weeks of casting significantly altered the maximum isometric twitch tension (-42.3%), contraction time (+17.1%), maximum tetanic tension (-38.1%), and half-fatigue time (+40.5%) in the soleus. The reinnervating soleus muscle appears to recover from the effects of casting sooner than the plantaris or gastrocnemius muscles.

Compensatory hypertrophy of the soleus in tumor-bearing rats.

Compensatory hypertrophy of the rat soleus was compared between normal rats (N) and rats bearing a non-metastasizing mammary tumor (TB). Two weeks after the tumor inoculation, introduced subcutaneously on the midline of the upper back, the two groups of rats underwent unilateral tenotomy of the plantaris and gastrocnemius muscles to induce functional overload or compensatory hypertrophy of the soleus. One week later, the body weight (BW), wet muscle weights (MW), percent of Type I (slow-twitch) and Type II (fast-twitch) muscle fibers and contractile parameters of the isometric twitch (Pt) and tetanic (Po) tensions were evaluated. The TB animals did not show any signs of cancer cachexia. The sham-operated control soleus muscles of the two groups were similar in wet MW, maximum isometric Pt and Po. The latent period (LP), the contraction time (CT), the half relaxation time (HRT) and the number of Type I (slow-twitch) fibers were increased significantly. The hypertrophied muscles in the N and TB rats showed significant declines in the maximum isometric Pt, compared to their respective controls. These data suggest that the compensatory hypertrophy of muscle is expressed similarly in both the normal and tumor-bearing rats but that it interferes with the generation of isometric twitch tension in the muscle.

Acetylcholine sensitivity and fibrillation potentials in electrically stimulated crush-denervated rat skeletal muscle.

Juxtamuscular electrodes were implanted unilaterally in six groups of adult female Wistar rats to evaluate the effect of chronic electrical stimulation (ES) during denervation and reinnervation of the rat soleus muscle. Two weeks later, the animals underwent bilateral crush-denervation of the sciatic nerve at the sciatic notch. Six additional groups served as normal controls. The soleus muscles in the crush denervated and control groups were stimulated unilaterally with a 4mA, 4msec duration current given at 10Hz continuously 8 hours each day for 5, 10, 15, 20, 25 or 30 days. At the end of each period, the soleus muscles were evaluated for the muscle weights, acetylcholine (ACh) sensitivity and fibrillation potentials (FPs). The normal muscles were unaffected by the stimulation. The denervated-stimulated soleus muscles were heavier at 10 days (p less than 0.05) and had fewer FPs after 5 to 15 days (p less than 0.01) of electrical stimulation than their matched denervated controls. The ACh sensitivity throughout the experimental period and the fibrillatory activity from 20 to 30 days post-crush were similar in the denervated and the denervated-stimulated muscles. In conclusion, ES reduced the degree of atrophy and the number of fibrillations of the soleus muscle in the denervation stage. However, it neither enhanced nor impaired the reinnervation of muscle.