Jaweed Mm

Effect of overwork during reinnervation of rat muscle.

Abstract Changes in muscle weights, protein content, and conduction latencies to gastrocnemius along with muscle weights of soleus and plantaris were investigated in adult rats at 72 hr, 1, 2, 3, 4, and 6 wk after bilateral sciatic nerve crush. The effect of overwork (induced by tenotomy of synergistic muscles) initiated in pre- and postreinnervation periods was evaluated in soleus and plantaris muscles. Evoked potentials by nerve conduction were lost at 72 hr and reappeared at the end of 3 wk. Muscle weight and protein content in the gastrocnemius decreased from 72 hr until 2 wk postdenervation. Muscle weights of plantaris and soleus followed the same trend. From 3 to 6 wk postdenervation all three muscles gained in weight and the protein content of gastrocnemius continued to increase to normal accompanied by shortened latency to indirect stimulation, although the latter returned only to 75% of normal. The return of nerve conduction 3 wk after neuronal damage indicates that functional reinnervation takes place between 2 and 3 wk after the nerve crush. The overwork, induced in the soleus and plantaris muscles by elimination of synergists, at 2 wk (Group II) and 3 wk (Group I) after denervation, showed contrasting results in protein content. Overwork in Group I significantly increased muscle weight, absolute amount of sarcoplasmic, myofibrillar and stromal proteins, and fiber diameters in both soleus and plantaris. Muscle weight, sarcoplasmic protein, and myofibrillar protein decreased in both muscles of Group II. However, fiber diameter exceeded control values only in the plantaris and was associated with an increased number of fibers exhibiting low myosin ATPase (pH 9.4) activity. The results of this study suggest that overwork begun within the period of reinnervation may be more beneficial than when initiated before this event.

Effect of swimming on reinnervation of rat skeletal muscle

There are no studies that define the optimum intensity or time to begin exercising reinnervating muscle. Through overwork of reinnervating muscle, accomplished by synergistic tenotomy, we developed a working hypothesis. This hypothesis was tested on a physiological model. In the present study, the sciatic nerve of five groups of rats was crushed. One group served as the control and the remaining animals were exercised by swimming with weights attached to their tails for one or two hours each day (early reinnervation group) or four weeks (late reinnervating group) after crush denervation. The evaluation of muscle weights, fibre types, and protein concentration indicate that intense swimming (two hours every day) does not enhance the repair of reinnervation muscle. An evaluation of total proteins suggests that a high workload may be hazardous in the early phase of reinnervation. This study tends to confirm the hypothesis that when there are too few contractile units, as presumably is the case in early reinnervation, exercise inhibits the reinnervation process.

Effect of activity and inactivity on reinnervating rat skeletal muscle contractility

Abstract Adult female rats underwent bilateral sciatic nerve crush for the purpose of evaluating the effect of activity and inactivity on the recovery of the contractile properties of the soleus and plantaris muscles. Treadmill training at 35% grade and bilateral cast immobilization of the hind limbs were started 2 or 3 weeks after sciatic nerve crush, when reinnervation is known to commence. The isometric twitch ( P t ) and tetanic ( P o ) tensions and time to peak tension ( C t ) were performed at an optimal length ( L o ) to give the maximum in vitro P t in a physiologic cell filled with aerated Ringers lactate solution ( p H 7.2) at 34 to 35°C. The plantaris P t , P o , and C t and soleus P o and C t were unaffected by the exercise, but recovery of the soleus P t was significantly impaired by the treadmill training. Cast immobilization delayed the recovery of the P t and C t more in the soleus than the plantaris. In conclusion, extremes of activity or inactivity retarded, but did not prevent, the recovery of the slow more than the fast muscle during reinnervation.

Prostaglandins in denervated skeletal muscle of the rat: Effect of direct electrical stimulation

Abstract The levels of prostaglandins, PGE 2 , PGE 2 -met (13, 14 dihydro 15-keto-PGE 2 ), PGF 2α and PGF 2α -met (13, 14 dihydro 15-keto-PGF 2α ) were measured by direct radioimmunoassay in the normal control, normal-stimulated, denervated control and denervated-stimulated gastrocnemius muscles of the rat. The normal ( n = 5 ) and bilaterally sciatic nerve crush-denervated ( n = 6 ) gastrocnemius muscles were stimulated with implanted juxtamuscular electrodes by 2–4 mA square wave pulses of 4 ms duration at 10 Hz continuously 8 h each day for 15 days. We found a significant increase ( P ) in the content of PGF 2α (78.2%) and PGF 2α -met (36.7%) in the normal-stimulated muscles, whereas denervation significantly increased (70–110%, P ) the levels of all prostaglandins studied. The stimulation of denervated muscles retarded the muscle atrophy (30.2%, P ) coincident with significant decreases in the content of PGE 2 and PGE 2 -met. Therefore, these data suggest that low frequency (10 Hz) electrical stimulation may retard the synthesis or the release of PGE 2 and its metabolites in the denervated skeletal muscle.

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.

Direct electrical stimulation of rat soleus during denervation-reinnervation.

The effect of direct, low-frequency electrical stimulation (at 10 Hz continuously 8 h daily) of muscle on isometric twitch contractile properties of adult rat soleus was observed during denervation and reinnervation. The normal and the bilaterally sciatic nerve crush-denervated groups were implanted with unilateral juxtamuscular electrodes to stimulate the soleus muscle in one limb. After 10, 15, 20, 25, and 30 days of electrical stimulation (2- to 4-mA pulses at 4 ms duration) the normal control, normal-stimulated, crush-denervated control, and crush-denervated-stimulated soleus muscles (N = 6) were evaluated in vitro by massively field stimulating the muscles in physiologic buffer (pH 7.2) at 23 to 24°C. The parameters of isometric twitch contraction measured were latent period (LP), maximum isometric twitch tension (Pt), contraction time (CT), maximum rate of isometric twitch tension (Vtmax), and half-relaxation time (HRT). In normal muscle, 25 and 30 days of electrical stimulation produced significant (P < 0.05) changes: muscle hypertrophy (26.5 and 16.6%, respectively), decline in the Pt (23.4 and 12.1%, respectively), and decrease in the (Vtmax) (17.3 and 21.6%, respectively). For the same periods, compared with the crush-denervated control, the crush-denervated-stimulated muscles also showed significant (P < 0.05) changes: prolongation of the LP. (22.9 and 26.5%), decline in the Pt (24.5 and 31.6%), and decrease in the Vtmax (27.7 and 33.3%). These results, therefore, suggest that the long-term (200 to 240 h) direct, lowfrequency (10 Hz) electrical stimulation may impair the mechanism of isometric twitch development in slow-twitch muscle of the rat. However, our study does not prove that this pattern of electrostimulation can significantly alter the course of self-reinnervation in 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.

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.

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)

Methylhistidine Changes in Tibialis Anterior Muscles of 6-Mercaptopurine-Treated Rats

1. Address correspondence to: M.M. Jaweed, Department of Rehabilitation Medicine, Jefferson Medical Center of Thomas Jefferson University, Philadelphia, PA 19107. 2.