Days Of Immobilization Research Articles

Tolerance and Cross-Tolerance to Stress-Induced Increases in Plasma Met-Enkephalin in Rats with Adaptively Increased Resting Secretion*

Plasma concentrations of both native (pentapeptide plus its sulfoxide) and peptidase-derivable (trypsin followed by carboxypeptidase-B) Met-enkephalin showed brisk increases in response to the stresses of immobilization, hemorrhage, and electric footshock in conscious, freely moving, adult male rats. Daily exposure to 150-min periods of immobilization resulted in a maintained increase in baseline plasma concentrations of native Met-enkephalin 21.5 h after the sixth day and a further increase after 39 days. The plasma native Met-enkephalin response to acute immobilization was attenuated on day 7 and completely absent on day 40. Unstressed rats showed a plasma native Met-enkephalin response to hemorrhage of 15% blood volume and a further increase in response to 25% hemorrhage. Immediately after initial acute immobilization or 6 days of daily immobilization when plasma native Met-enkephalin was elevated but the response to acute immobilization was attenuated, plasma native Met-enkephalin responses to hemorrhage were also attenuated. Rats that had been immobilized daily for 40 days and showed no plasma native Met-enkephalin response to acute immobilization also showed no responses to hemorrhage. After 39 days of immobilization when there was no plasma native Met-enkephalin response to acute immobilization, there was also no response to footshock. Thus, development of tolerance or adaptive loss of plasma native Met-enkephalin response to immobilization with repeated exposure to this stressor is associated with cross-tolerance or adaptive loss of the responses to the stresses of hemorrhage or electric footshock. Development of tolerance and cross-tolerance of plasma responses of peptidase-derivable Met-enkephalin paralleled that of native Met-enkephalin. Thus, adaptation of plasma Met-enkephalin responses to repeated exposure to a stressor included both increased resting secretion and decreased acute responses to homotypic or novel stressors.

Value of Continuous Passive Motion in Total Knee Arthroplasty

Two methods of rehabilitation after 91 total knee arthroplasties in 74 patients were reviewed. Patients in each group were well matched for age, sex, and diagnosis. Forty-four knees in 39 patients were treated with conventional physiotherapy, consisting of 3 days of immobilization followed by a program of active assisted range-of-motion exercises. Forty-seven knees in 41 patients were placed in a continuous passive motion machine immediately after operation. Other aspects of preoperative, intraoperative, and postoperative care were identical in both groups. Patients in the continuous passive motion group were found to have a lower incidence of complications, especially of wound healing problems and thromboembolic disease. Analgesic use in patients in the continuous passive motion group was reduced. Straight leg raising was achieved slightly earlier in patients in the continuous passive motion group (4.9 days) compared with patients not treated with continuous passive motion (5.2 days). Although the range of motion of the knee at discharge from the hospital in patients in the continuous passive motion group was greater (91 degrees) compared with patients not treated with continuous passive motion (81 degrees), the range of motion in both groups at ultimate follow up was equivalent. However, when knee-rating scores were considered, patients treated with continuous passive motion averaged 9 points higher on a 100-point scale than patients not treated with continuous passive motion. In addition, the length of hospital stay for patients in the continuous passive motion group was 2.1 days shorter. We concluded that continuous passive motion was an effective adjunct to physiotherapy in the postoperative care of patients undergoing total knee arthroplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin action in human thighs after one-legged immobilization.

Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine release of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I, lactate release was significantly higher in the immobilized than in the control thigh. Seven days of one-legged immobilization causes local decreased insulin action on thigh glucose uptake and net protein degradation.

Immobilization leads to early changes in hydrostatic pressure of bone and joint. A study on experimental osteoarthritis in rabbits.

Immobilization of a rabbit leg in extension results in the early development of an aseptic inflammation, synovial effusion and stiffening, and subsequent osteoarthritis of the knee. To study the pathogenesis of this experimental osteoarthritis, the hydrostatic pressures were measured in the knee, and distal metaphysis and diaphysis of the femur, after different periods of immobilization in 28 rabbits and eight control rabbits. A marked rise in pressure was registered early in the femoral metaphysis, diaphysis and especially in the knee. The maximal pressures were found after two days of immobilization in the metaphysis and seven days in the knee. During the next two weeks the pressures decreased slowly towards the normal values. These changes were related to the thickening and stiffening of the knee. The increased pressure in the bone and joint may be an important pathogenetic factor in the experimental osteoarthritis following immobilization. Measurements of the hydrostatic pressure may be a valuable parameter aiding the development of better preventive and curative methods in arthritis and osteoarthritis.

Actin synthesis rate and mRNA level increase during early recovery of atrophied muscle.

The purpose of this study was to correlate actin synthesis rate and alpha-actin mRNA level in the gastrocnemius-plantaris muscles of limbs during their recovery from 7 days of immobilization in 200- to 280-g female rats. The fractional synthesis rate of actin in control muscle was 1%/day. Actin synthesis rate was 33% of control level at the 7th day of hindlimb immobilization, returned to control value at the 2nd recovery day, and was three times higher than control on the 4th day of recovery. The alpha-actin mRNA was 53% of control at the 7th day of immobilization, and its increase during the 1st 2 recovery days paralleled the increase in actin synthesis rate; this suggests that pretranslational mechanisms caused the initial increase in actin synthesis. Further increases in actin synthesis from the 2nd to the 4th day appear to be under translational control, since actin synthesis was 300% of control on the 4th recovery day and alpha-actin mRNA was only 128% of control.

A prospective study identifying the sensitivity of radiographic findings and the efficacy of clinical findings in carpal navicular fractures

Carpal navicular fracture is the most common wrist bone fracture. Improper diagnosis and inadequate treatment result in potentially serious complications, including delayed fracture union, pseudoarthrosis, avascular necrosis, and wrist instability ultimately leading to deformity and osteoarthritis. Initial radiographs do not always demonstrate a discernible fracture line. To better define the frequency of initially negative radiographs of the navicular associated with true navicular fractures, and to test the efficacy of the three clinical signs (snuffbox tenderness, pain with supination against resistance, and pain with longitudinal compression of the thumb toward the navicular), a prospective study of 85 patients who presented to the emergency department during a four-year period with a mechanism of injury suggesting possible navicular injury was conducted. Forty-five patients had no demonstrable fracture or instability on initial examination or during the follow-up period. Forty patients ultimately were shown to have navicular fractures. Patients with negative radiographs and positive clinical findings were reevaluated after ten to 14 days of immobilization. Thirty-two patients had fracture lines visible on initial radiographic examination, and eight had lucent fracture lines demonstrated after ten to 14 days of immobilization. Snuffbox tenderness had a sensitivity of 100% and a specificity of 98% for fracture; supination against resistance had a sensitivity of 100% and a specificity of 98%; and longitudinal compression of the thumb had a sensitivity of 98% and a specificity of 98%. Chi-square analysis revealed a P value less than .001 for each of the three clinical maneuvers. This study reports a 20% occurrence of initially false-negative radiographs, which is higher than previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome c protein-synthesis rates and mRNA contents during atrophy and recovery in skeletal muscle.

It is known that immobilization of the rat hindlimb by plaster casting leads to muscle atrophy and loss of muscle protein. In the present study, immobilization of the rat hindlimb for 6 h resulted in a significant 27% decrease in the absolute rate of cytochrome c synthesis in the red quadriceps muscle, without any change in the relative amount of cytochrome c mRNA. Cytochrome c mRNA in normal red quadriceps muscle was observed to be of four different lengths (1400, 1050, 650 and 580 bases). After 7 days of immobilization, the absolute rate of cytochrome c synthesis remained depressed and cytochrome c mRNA decreased by 40%; each of the cytochrome c mRNAs decreased, with a preferential disappearance of the 1050- and 1400-base lengths. Immobilization was ended on day 7, and the atrophied muscle was allowed to recover. At day 4 of recovery, the absolute rate of cytochrome c synthesis was 92% higher and the amount of cytochrome c mRNA had returned to control values. The abundances of the 1050- and 1400-base cytochrome c mRNAs had increased more than the shorter cytochrome c mRNAs, so that they were higher than control values. It appears that acute decreases in contractile activity of the red quadriceps muscle alter cytochrome c synthesis rates via translational or post-translational mechanisms, whereas chronic periods of modified contractile activity alter its synthesis rate via pre-translational mechanisms.

Adrenaline and stress-induced increases in blood pressure in rats.

Stress was induced by immobilizing the hind limbs of rats for 12 days and housing the rats in individual cages. Control rats were housed in groups without immobilization. Blood pressure and heart rate were measured through an indwelling carotid cannula. After 10 and 12 days of immobilization and isolation, the stressed rats had significantly higher blood pressures (ca. 10 mmHg) and higher cardiac adrenaline levels (ca. 90%). After adrenal medullectomy cardiac adrenaline levels were markedly reduced in both stressed and control rats. Furthermore, the stressing procedure did not cause a rise in blood pressure in adrenal-medullectomized rats. Desipramine HCl (2 mg/kg per day), administered orally to block the neuronal uptake of adrenaline, prevented the elevation in blood pressures and cardiac adrenaline levels. Propranolol HCl (2.8 mg/kg per day), orally, also prevented the rise in blood pressure. The results are consistent with the hypothesis that activation of facilitatory prejunctional beta-adrenoceptors on sympathetic nerves by neuronally-released adrenaline may be responsible for the raised blood pressure.

Levels of blood-bourne factors and cytosol glucocorticoid receptors during the initiation of muscle atrophy in rodent hindlimbs.

When only 1 hindlimb of the adult mouse was immobilized for 13 h, the immobilization-induced failure of insulin to stimulate 2-deoxyglucose uptake was observed in the immobilized soleus muscle. 2-deoxyglucose uptake was unchanged in the contralateral, nonimmobilized muscle. In the rat, protein synthesis rates decreased in the one immobilized limb as compared to rates measured in the contralateral nonimmobilized limb of the same animal. The synthesis rates in the contralateral nonimmobilized limb of a rat with one immobilized limb were not significantly different from rates of muscle protein synthesis observed in rats with no hindlimb immobilization. Specific binding of 3H-dexamethasone, as determined by exchange assay in the gastrocnemius muscle cytosol, increased after 7 days of immobilization, but not after only 6 h of immobilization. Changes in the level of blood-bourne factors or in cytosolic glucocorticoid levels do not by themselves initiate muscle atrophy in immobilized rodent limbs.

Changes in actin synthesis and alpha-actin-mRNA content in rat muscle during immobilization.

The fractional rates of actin synthesis in adult rat gastrocnemius muscle from control and 6-h hindlimb-immobilized animals were determined by the constant-infusion technique. The rate of actin synthesis in gastrocnemius muscle was significantly decreased from control values during the 6th h of hindlimb immobilization. The content of alpha-actin-specific mRNA was then estimated in adult rat gastrocnemius muscle from control, 6-h, 72-h, and 7-day immobilized animals by "dot blot" hybridization. RNA extracted from control and immobilized animals was secured on nitrocellulose filters and hybridized to 32P-labeled plasmid p749 (containing a cDNA sequence produced from rat alpha-actin mRNA). The relative content of alpha-actin-specific mRNA in gastrocnemius muscle was significantly decreased at 7 days of immobilization but not at 6 or 72 h of immobilization. It is concluded that a change in the content of alpha-actin mRNA does not contribute significantly to the rapid onset of the decrease in actin synthesis rate observed after 6 h of immobilization. An alteration in the translation of alpha-actin-specific mRNA must occur to account for the early decline in actin synthesis during immobilization.

Inflammatory involvement in rabbit knee following immobilization and resulting in osteoarthritis.

The inflammatory involvement of the synovium in immobilization-induced experimental osteoarthritis in rabbit knees has been investigated. One knee of each of 33 rabbits was immobilized for up to 5 weeks in extension and then allowed to remobilize for up to 8 weeks. Histological examination revealed the presence of marked inflammatory changes in the synovium which were evident after 4 days of immobilization. These were characterized by a rapid proliferation of synovial lining cells followed by mononuclear cell infiltration and fibrosis. The synovial cell proliferation decreased during the latter part of the immobilization period but reappeared in a more severe form during remobilization, at which time gross changes could be demonstrated in the joints. Synovial fluid levels of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were elevated on day 3 and day 10 but had returned to baseline levels by day 24 of immobilization. Treatment of the animals with the nonsteroidal anti-inflammatory agent flurbiprofen (10 mg/kg/day) had neither a beneficial nor a deleterious effect on any of the parameters measured. This study has shown that immobilization-induced experimental osteoarthritis in rabbits is associated with a marked inflammatory component and that during the remobilization phase of this model the inflammation appears to be a secondary event.

Is limb immobilization a model of muscle disuse?

Limb immobilization is often used as a model of disuse-atrophy of skeletal muscle. Because the degree of atrophy is somewhat dependent on the length at which the muscle is immobilized, information regarding the effect of immobilization at various joint positions on the electrical activity of slow and fast muscles should provide a better understanding of the role of “use-disuse” in determining the degree of atrophy. In this study, the soleus muscle (SOL) and medial gastrocnemius muscle (MG) of adult female rats were chronically implanted with bipolar recording electrodes. The hind limbs were immobilized bilaterally using an external brace such that the muscles were fixed in a shortened, neutral, or lengthened position. Electromyograms (EMGs) of the SOL and MG were recorded simultaneously during a 15-min period each hour for 24 consecutive hours 3 and 9 days after electrode implantation, and 7, 17, and 28 days after immobilization. The weights of both muscles decreased significantly ( P < 0.05) when fixed in a shortened or neutral, but not in a lengthened position after 28 days. As indicated by the 24-h integrated EMG (IEMG), the SOL, which was more active than the MG in unrestrained rats, showed the greatest decrease in postimmobilization activity. After 28 days of immobilization in a shortened position, the IEMG of the SOL and MG was significantly reduced ( P < 0.05) by 77 and 50%, respectively. The IEMG of the SOL immobilized in a neutral position decreased 50% whereas no change was seen in the MG. There was no significant change in the IEMG for the SOL or MG fixed in a lengthened position. These data suggest that the EMG was dependent on the type of muscle and the length of fixation. Furthermore, it appeared that the degree of atrophy was not related closely to changes in the IEMG suggesting that limb immobilization was not necessarily a model of “disuse”.

3H]proline incorporation and hydroxyproline concentration in articular cartilage during the development of osteoarthritis caused by immobilization. A study in vivo with rabbits.

Proline metabolism in vivo was studied during the development of immobilization osteoarthritis in rabbits. Collagen content was measured as the hydroxyproline concentration of the tissue in question. The incorporation of [3H]proline was used as the indicator for total protein synthesis; collagen synthesis rate was estimated from measurements of the specific radioactivity of hydroxyproline. Cartilage samples from knee and hip joints were analysed after 3, 7, 11, 18, 35 and 56 days of immobilization. The total protein and collagen synthesis rates of the immobilized legs increased and reached a maximum after 11-35 days. Although they decreased thereafter, these rates remained elevated to the end of the experiment. A slight increase in the synthetic activity of the non-immobilized contralateral legs was also detected after 7--18 days of immobilization. The isotope incorporation was markedly higher in tibial marginal tissue than in weight-bearing cartilage. In spite of the increased synthesis, no clear changes were found in the collagen content of the tissues studied during the experiment.

Glycosaminoglycan metabolism of the medial meniscus, the medial collateral ligament and the hip joint capsule in experimental osteoarthritis caused by immobilization of the rabbit knee.

A study was made of glycosaminoglycan metabolism in experimental osteoarthritis caused by immobilization of the rabbit knee in extension. Samples from the medial meniscus, the medial collateral ligament of the knee and the hip joint capsule were obtained and analysed after 2, 6, 10, 17, 30 and 87 days of immobilization, samples from the mobile limb serving as controls. The tissue concentrations of glycosaminoglycans were determined from measurements of hexosamine and uronic acid after prior papain proteolysis and subsequent purification. The uptake of 35S-sulphate (DPM/microgram hexosamine) was used as an indicator of the synthesis rate of sulphated glycosaminoglycans. In both early and advanced immobilization osteoarthritis, the synthesis rate and the content of glycosaminoglycans were increased in all tissues.

The effects of cortisone treatment on the protein turnover of the soleus muscle after immobilization.

The glucocorticoid hormones appear to play an important role in mobilizing body proteins to facilitate gluconeogenesis in response to falling concentrations of plasma glucose. It has previously been shown (Goldberg & Goodman, 1969) that denervated skeletal muscle is more susceptible to the catabolic effects of cortisone. However, denervation is a rather drastic means by which to render a muscle inactive. In addition t o the deprivation of possible neurochemical influences, the presence of spontaneous electrical activity (Thesleff, 1963) and possible increased passive stretching of the tissue (Sola et al., 1973; Goldspink, 1978) make the denervated preparation a complicated system for studying inactivity. In the present investigation we have rendered the soleus muscle of young rats (approx. 40g pre-operatively, CD strain, Charles River U.K. Ltd.) inactive without depriving the muscle of its innervation. This was achieved by placing a plaster-of-Paris cast around the ankle joint of one hind limb. With thefoot restrained in the extended position the soleus muscle was immobilized in a fully shortened and unstretched state (Goldspink, 1977). We then examined changes in the size and protein turnover of the soleus muscle after 4 days of such immobilization. The changes in these NaCI-injected animals were compared with those in similar animals that had received two injections of cortisone acetate (0.25mg/day per lOOg body wt.) on each of the 4 days of immobilization. With this less complicated system, we re-examined the question of whether contractile activity protects muscle from the actions of catabolic hormones. In addition we have attempted to elucidate some of the mechanisms involved in such a response. The excess cortisone did not affect the growth rate of these young rats, as evidenced by similar increases in the body weights (approx. 2g/day) of both NaC1-treated and hormone-treated animals. Immobilization of the soleus muscle caused a significant decrease in the size of the tissue, compared with non-restrained controls (Table 1). These findings are in excellent agreement with a previous study (Goldspink, 1977), where it was shown that the immobilized soleus in such young rats undergoes a true atrophy and not simply decreased rates of growth. Since protein remained 16-17% of the muscle mass, changes in total protein closely paralleled the changes in muscle weight after immobilization (Table 1) . The presence of cortisone did not, however, appear t o have any additional influence on the weight of the immobilized muscle, nor indeed on the internal, non-restrained controls (Table 1). However, after cortisone treatment the protein composition fell to only 12% of the wet weight. Hence in the presence of excess cortisone, there was some fluid retention (Forsham, 1968) contributing to the unchanged wet weight of the immobilized tissue. This latter finding was not, however, true in the case of the control tissue on exposure to the hormone. So although cortisone had not affected the wet weight of the immobilized muscle, it had caused a greater net loss of protein (Table 1). Average rates of protein synthesis and protein breakdown were measured in vitro by the slightly modified method (Goldspink, 1978) of Fulks et al. (1975) to explain the changes in protein concentrations after immobilization, in the presence or absence of cortisone. Immobilization in the absence of excess hormone caused both a significant decrease in protein synthesis and an increase in protein degradation (Table 1). Thesecomplemen-

Changes in 35S-sulphate uptake in different tissues in the knee and hip regions of rabbits during immobilization, remobilization the development of osteoarthritis.

In order to observe phenomena accompanying the development of osteoarthritis of the rabbit knee, consistently appearing within 4-6 weeks as a consequence ofimmobilization of this joint, studies on 35S-sulphate (Na2 35SO4) uptake were carried out. The investigation suggests that immobilization of the knee leads within 2-4 weeks to increased sulphate uptake in bone, cartilage and ligaments in the knee region and in the hip (not immobilized) of the same leg. The first marked changes in 35S-sulphate uptake were found in the ligaments and the articular cartilage as early as after 4 days of immobilization.

The effect of fluoride alone or fluoride followed by calcium and vitamin D on disuse osteoporosis of the rat tail vertebrae.

The therapeutic effect of fluoride alone or fluoride followed by calcium and vitamin D administration on the osteoporosis induced by immobilization of the rat tail vertebrae was investigated. Tail immobilization was carried out by musclectomy and tendectomy. After 60 days of immobilization, the vertebrae were examined for bone mass, breaking strength, ash percentage and Ca, P and F content. NaF or Ca and vitamin D as separate treatments improved the osteoporosis induced by immobilization. The effects of NaF treatment were more pronounced than those of Ca and vitamin D. NaF and NaF followed by Ca and vitamin D produced a similar degree of improvement in breaking strength. The fact that fluoride and calcium and vitamin D were administered separately and sequentially may explain the absence of a synergistic effect.

The effect of short-term immobilization on the rabbit knee joint cartilage. A histochemical study.

Rabbit knee joints were immobilized in the extended position for 1 to 6 days, and examined by means of histochemical techniques. In the articular cartilage matrix, the earliest change was the loss of affinity for metachromatic stains, confirming earlier observations. The affinity of cartilage for high iron diamine and alcian blue stains was also diminished, although less dramatically; these stains demonstrated the concentration of glycosaminoglycans more accurately than metachromatic stains. With the colloidal iron method, changes were seen in the chondrocytes before there was any loss of affinity for metachromatic stains. Following only 1 or 2 days of immobilization, the chondrocytes in the gliding surface of the joint stained intensely with colloidal iron whereas those in the controls stained very minimally.

Complex Dislocation of the Metacarpophalangeal Joint

The operative findings and pathological anatomy in nine patients with complex metacarpophalangeal dislocations correlated well with dissections in fresh cadaver hands. The single most important element preventing reduction is interposition of the volar plate between the base of the proximal phalanx and the head of the metacarpal. Of importance is an understanding of the three sets of transverse ligaments and their relationship to the volar plate: (1) the natatory ligament, (2) the superficial transverse metacarpal ligament, and (3) the deep transverse metacarpal ligament. Early active motion was encouraged, commencing immediately following open reduction, and resulted in a full range. In one patient, ten days of immobilization caused residual restriction of motion.

Effect of increased and diminished functional loading with physical work on the reproductive function of rats: physical work, hypodynamics and reproduction.

Summary. A total of 150 Wistar albino male and female rats were divided into three groups: (1) exercised by running (treadmill), (2) physiologically immobilized, and (3) controls. Following 108 days of immobilization, nine colonies were formed, each colony consisting of one male rat with four females. The combinations were: trained male with trained females, trained male with immobilized females and trained male with control females. The same three combinations were arranged with immobilized and with control males. The rats were 6½ months old at the time of forming the colonies. The results showed that the trained rats were in the best, and the immobilized in the poorest breeding condition. Whereas immobilized male and female rats in homogeneous colonies had the lowest fertility, in heterogeneous colonies with active partners (control or trained animal) they showed a high degree of fertility. The active animal, irrespective of sex, succeeded in activating and impregnating its inactive partner. The highest mortality of the progeny was observed in colonies of immobilized animals and the lowest in colonies which included exercising animals.