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Dependence of cyclopiazonic-acid-induced muscle contractures on extracellular Ca2+.

Inhibition of Ca2+ uptake by the sarcoplasmic reticulum decreases cytosolic Ca2+ clearance and also triggers Ca2+ influx in response to Ca2+ store depletion. The role of extracellular Ca2+ in the contractures evoked by cyclo-piazonic acid (CPA) and thapsigargin (TG), Ca2+ pump inhibitors, was assessed in mouse diaphragm. At 3-100 microM, CPA elicited a rapid-onset contracture followed by a large elevation of muscle tone, which corresponded temporally to the monophasic slow contracture evoked by TG (1-30 microM). Irrespective of the differences in profiles, contractures were prevented and inhibited by the removal of extracellular Ca2+, but not by nicardipine and SK&F96365, blockers of voltage-gated (L-type) and receptor-operated Ca2+ channels. Mn2+ and Ni2+ preferentially depressed the fast-phase contracture, whereas long-term pretreatment with LY294002, U73122, and 2-aminoethoxydiphenylborance, inhibitors of phosphatidylinositol kinase, phospholipase C, and inositol trisphosphate receptors, suppressed the slow-phase contracture. When contracture was inhibited, the twitch response remained augmented and prolonged by CPA and TG, indicating that the inhibition was not due to malfunction of the contractile apparatus. For preparations incubated in Ca2+-free medium containing CPA, a monophasic fast upstroke of muscle tone developed as extracellular Ca2+ was restored. The results suggest that the bimodal contracture induced by CPA is mediated by the recruitment of distinct Mn2+- and U73122-sensitive Ca2+ entries. The ongoing two-component Ca2+ entries might merge if the muscle preparation was preconditioned with CPA in Ca2+-free medium to deplete cellular Ca2+ stores.

Animals↗

Ryanodine and the calcium content of cardiac SR assessed by caffeine and rapid cooling contractures.

The ability of rabbit ventricular muscle sarcoplasmic reticulum (SR) to accumulate and retain Ca during Na-free perfusion was assessed using caffeine contractures and rapid cooling contractures (RCC). Muscles were exposed to a Na-free medium for 15 min, during which time a transient contracture developed and relaxed back to the resting tension level. Muscles were then either exposed to 20 mM caffeine or rapidly cooled to less than 5 degrees C, both of which produced large contractures. The magnitudes of those contractures are believed to be a relative index of SR Ca content. Reduction of extracellular [Ca] from 2 to 0.2 mM did not significantly alter the magnitude of either Na-free caffeine contractures or RCC. These are not the maximum contractures that can be obtained. The possibility that low extracellular [Ca] ([Ca]o) may increase passive Ca permeability is suggested in explanation of this effect. After equilibration with 100 nM ryanodine, both Na-free caffeine contractures and RCC are virtually eliminated. This suggests that even if the SR could accumulate Ca during the initial Na-free exposure in the presence of ryanodine, it could not retain that Ca in Na-free medium. It is proposed that the sarcolemmal Ca pump can extrude Ca from the cells at a rate sufficient to deplete the ryanodine-treated SR. When removal of Na was accompanied by increase of [K]o (to 12, 20, or 30 mM), the Na-free RCC were enhanced. Increasing [K]o during Na-free superfusion in the presence of ryanodine resulted in demonstrable RCC that were graded with [K] and completely suppressed by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers.

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.

Adenosine Triphosphate↗

Factors affecting high-potassium-induced contracture of guinea-pig vas deferens.

Some factors which may influence the high-K-induced contracture of guinea-pig vas deferens were studied. Portional variations were observed in the height of tonic contraction but not in phasic contraction; tonic contraction was higher on the epididymal side and lower on the prostatic side. Circular muscle showed contracture similar to that of longitudinal muscle in the shapes of the contracture and the tendency to portional variations. Histological variations of muscle structure could not explain these variations. Electrical stimulation of the preparation by continuous weak AC current induced contracture similar to the high-K-induced contracture. The contracture evoked by AC stimulation was blocked by TTX and phentolamine. Blocking agents of possible transmission involved in high-K depolarization did not alter the relation of phasic and tonic contractions, although some of the drugs showed an inhibiting and some an enhancing effect. In isotonic observations, tonic contraction was highly sensitive to load and was elevated with a low load and depressed with a high load. It was revealed that the phasic and tonic contraction of high-K-induced contracture was a direct reaction of longitudinal muscle, although various factors could have had some influence on the contracture.

Animals↗

Effects of conditioning depolarization, repriming, and external calcium reduction on the potassium contractures in frog single twitch muscle fibers.

The inactivation of potassium (K) contractures induced by prolonged conditioning depolarization and repriming after 190 mM K+ contractures were studied at both room and low temperatures using frog single twitch muscle fibers. Effects of conditioning K+ depolarization and external Ca2+ reduction on the biphasic K contractures were also studied. When the conditioning depolarization with 15-30 mM K+ was prolonged, the peak tension of test 190 mM K+ contractures was inhibited in parallel with the shortening of plateau duration at both room and low temperatures. Such parallel changes were also observed during the early stage of repriming after 190 mM K+ contracture at both temperatures. On the other hand, the peak tension of the secondary component of the test 80 mM K+ contractures was rather potentiated by the conditioning depolarization, even though the time course of the component was markedly shortened. The foregoing changes were also illustrated in a diagramatic way. These results suggested that the peak tension and the time course of the test K contractures after conditioning depolarization and during repriming may be determined by a balance between the activation and the inactivation processes of the contractures. This view is supported by the results obtained under conditions in which the concentration of external Ca2+ was reduced. Furthermore, based on additional experimental results, it was suggested that the initial component is not accompanied by an inactivation process and that Ca uptake by sarcoplasmic reticulum may partially contribute to determining the spontaneous relaxation phase of the secondary component, at least at room temperature.

Animals↗

Some features of the electrically induced contracture in the frog skeletal muscle: reexamination of the post-anodal inhibition.

Some features of the electrically induced contracture were investigated by means of the partition polarization method in the toe muscles of a bullfrog. Under the current clamp condition and in the presence of tetrodotoxin, a biphasic contracture was induced by strong depolarizing pulses, 1 sec, in duration. The contracture was depressed either by lengthening the pulse interval or by reducing the external calcium concentration. Furthermore, the contracture was augmented by applying conditioning depolarization and inhibited by conditioning hyperpolarization without accompanying any noticeable changes in the test depolarization. Caffeine at a concentration of 1 mM depressed the inhibitory effect of pre-hyperpolarization. Strong hyperpolarizing pulses had no effect on the caffeine contracture, whereas a similar pre-hyperpolarization markedly suppressed the phenomenon on the post-contracture potentiation of twitch, induced by a powerful sustained depolarization. From these results it was suggested that calcium ions in the vicinity of the myoplasmic site of the transverse tubular membrane may play some role in generating and regulating the contracture. The possibility of direct contribution of calcium entering from the cell exterior in contracture generation, especially for the slow component, and its regulation was also discussed.

Animals↗

Effects of dichlorobenzamil, a sodium-calcium exchange inhibitor, on the calcium paradox and the sodium withdrawal contractures of frog atrial muscle.

1. The effects of dichlorobenzamil (DCB), an amiloride derivative and potent inhibitor of Na-Ca exchange in cardiac sarcolemmal vesicles and isolated cardiac myocytes, were investigated in two paradigms involving Na-Ca exchange, namely the Ca2+ paradox and the Na+-withdrawal contractures of frog atrial muscle strips. 2. Pretreatment with DCB (10-100 microM) inhibited in a dose-dependent manner the contractures elicited by reexposure of the atrial strips to the control Ringer solution after a 5-20 min equilibration with a Ca2+-free saline (Ca2+-readmission contractures; Ca2+ paradox). These contractures were not inhibited, however, when DCB was applied after the preparation had been exposed to the Ca2+-free saline, but before the reexposure to the control Ringer solution. 3. DCB (10-100 microM) did not inhibit the contractures elicited by Na+-deficient saline (Na+-withdrawal contractures) in atrial strips pretreated or not with acetylstrophantydin. This result suggests that, under our experimental conditions, DCB failed to substantially inhibit the Ca2+ influx mediated by Na-Ca exchange. 4. The duration of the plateau of the action potentials of atrial cells equilibrated with Ca2+-free saline was reduced from 1.42 +/- 0.27 s to 0.61 +/- 0.13 s by 50 microM DCB (P less than 0.001). This was attributed to blockade of Na+ currents through modified L-type Ca2+ channels. 5. It is proposed that the shortening of the Na+-dependent action potentials can account for the inhibition of the Ca2+-readmission contractures, because these contractures have a steep dependence on the Na+ influx and intracellular Na+ accumulation that occurs during the Ca2+-free period. 6. The results of this study support the conclusion that DCB has multiple effects on heart muscle, including a potent blockade of Ca2+ channels, and its use as a selective inhibitor of Na-Ca exchange in cellular systems is unwarranted.

Amiloride↗

[Comparative characteristics of depolarization (potassium) and acetylcholine contracture of Lampetra fluviatilis lamprey phasic muscle].

Acetylcholine (Ach) contractures of thin bundle from m. longitudinal linguae of the lamprey differs by several parameters from depolarization (potassium) contracture, although Ach similar to K ions totally depolarizes the surface membrane of muscle fibers. Maximum tension of Ach contracture is 30--100% higher than that of K contracture, maximum of both contractures being observed at the same membrane potential level (approximately -10mV). The rate of rise of Ach contracture is 10 times higher, whereas the latent period is 3 times shorter as compared with the same parameters of K contracture. At higher Ach concentrations (10(-5)--10(-4) g/ml) the latent period of contracture is shorter than that of depolarization.

Acetylcholine↗

A method to evaluate contractures effects during the gait of children with Duchenne dystrophy.

Joint contractures are the second major impairment affecting the locomotor system of children with Duchenne muscular dystrophy (DMD). While the negative influence of joint contractures has been documented, the passive moments produced by joint contractures could benefit the gait of patients with muscle weakness. We describe a biomechanical model that quantifies the mechanical contribution of ankle and hip flexion contractures to the gait of DMD children. Kinematic and kinetic parameters were measured under the same experimental conditions during the gait and passive resistance assessment of two subjects: one healthy child as a control, and one child with DMD. The child with DMD had a plantar flexion contracture and a greater ankle stiffness coefficient than the control child. During gait, the contribution of the ankle passive moment to the net moment was more important for the child with DMD than for the control child. At the hip, passive joint moments and passive moment contribution were more important for the control child but this was not related to the presence of hip flexion contracture. These preliminary results suggest the model might be used to evaluate contractures effect on a larger cohort of subjects.

Ankle Joint↗

Cadmium withdrawal contractures in rat soleus muscle fibres.

Transient "Cd2+ withdrawal" contractures, with amplitudes of < or =60% peak tetanic tension, were seen when > or =3 mM Cd2+ was removed, after exposures lasting > or =5 min, from solutions bathing rat soleus fibres at 22 degrees C with Cl- as the major external anion. The minimum free [Cd2+] for withdrawal contractures was reduced twofold when the external anion was SO4(2-). Withdrawal contractures were not seen after removal of 3 mM Co2+, Zn2+ or La3+ and were not observed in rat extensor digitorum longus fibres. The contractures were not due to depolarization (membrane potential, Vm, did not change during Cd2+ removal) or to an influx of external Ca2+ (the transient tension increase was recorded when solutions either lacked Ca2+, or contained 2 mM Co2+). Cd2+ withdrawal contractures were abolished by inactivation of excitation-contraction coupling (ECC) following depolarization in 40 mM K+ for 20 min, and recovered from inactivation at the same time as twitch and tetanic contractions with repriming of ECC. Withdrawal contractures were depressed by agents that depress ECC, i.e. low [Ca2+], 2 mM Co2+, 30 mM Ca2+, 30 mM Mg2+ and 50 microM nifedipine. The results support a hypothesis in which withdrawing Cd2+ from the external solution induces a contracture by activating the voltage sensor for ECC.

Animals↗

A study of the repeatability of the diagnosis of Dupuytren's contracture and its prevalence in the grampian region.

200 consecutive geriatric patients over 60 years of age (100 men and 100 women) were examined for signs of Dupuytren's contracture and questioned about certain risk factors thought to be associated with the disease. Each patient was examined, independently, by two orthopaedic surgeons. The diagnosis of Dupuytren's contracture was established by the finding of a thickening in the palm fixed to the palmar fascia as a nodule or band. However each patient was also examined for skin tethering, flexion contractures of digits and knuckle pads. The results were then analysed and a Kappa test performed on the data to assess the inter-observer variability in eliciting the signs of Dupuytren's contracture. Using the Kappa test agreement between the two observers was found to be, on average, 1.0 for observing flexion contractures, 0.8 for observing skin tethering, 0.7 for observing palmar nodules and 0.7 for observing knuckle pads. The two observers both made the diagnosis of Dupuytren's contracture in 21% of women and 39% of men. These figures are high compared with previously published data from other centres and confirm the locally held belief that Dupuytren's contracture is particularly prevalent in North-east Scotland.

Aged↗

Leg contracture in mice after single and multifractionated 137Cs exposure.

This is a report of studies of time-dose relationships for post-irradiation leg contractures in mice. The isoeffect doses for various degrees of contracture, measured 250 days after irradiation, increased with the number of fractions, but not with the overall treatment times, throughout 30 days. The isoeffect curves relating the total doses for given levels of responses to the doses per fraction were steeper for leg contractures than for acute skin reactions. The alpha/beta ratios ranged from 1.4 to 5.0 Gy, depending on the degrees of contracture. They were less than the 7.5 to 50 Gy for acute skin reactions as determined in previous experiments using the same animals and irradiation systems. Thus, the data resembled those from other slowly-responding normal tissues such as the spinal cord, kidney and lung. The leg contracture consisted of dermatogenic, myogenic, and arthrogenic components; after the mice were sacrificed there was residual contracture following removal of the skin and muscle. Inhibition of bone growth accounted for only a small proportion of the contracture. The overall response reflected responses of several tissue types.

Animals↗

Dupuytren's contracture: morphological and biochemical changes in palmar aponeurosis.

The palmar aponeurosis removed from ten patients with Dupuytren's contracture was studied using morphological and biochemical approaches. The histological characteristic of Dupuytren's contracture is the presence of numerous nodules among the lamellar structures of the collagen fibres. In the nodules, there are many active fibroblasts which are surrounded by immature fibres and metachromatic substances demonstrated by toluidine blue staining. Ultrastructurally, the active fibroblasts have the characteristics of myofibroblasts, as previously reported by Dr. Gabbiani. We found that some fibroblasts have intracellular collagen fibrils in the cytoplasm. When assayed by Siegel and Martin's method, lysyl oxidase activity of the palmar aponeurosis was significantly higher in Dupuytren's contracture than in normal hands. Biochemical studies such as electrophoretic analysis of mucopolysaccharides, determination of uronic acid and collagen contents were undertaken to compare the aponeurosis of Dupuytren's contracture with normal cases. The uronic acid contents were higher in Dupuytren's contracture than in the controls. However, no difference between the two groups was found in the collagen contents and in the composition of the mucopolysaccharides. These characteristic features; existence of myofibroblasts and intracellular collagen fibrils and increase in the activity of lysyl oxidase probably play a significant role in the establishment of flexion contracture of the fingers in Dupuytren's contracture.

Adolescent↗

Imaging factors related to rotator cuff tear in patients with deltoid contracture.

BACKGROUND: Bony deformity and muscular malfunction around the shoulder induced by deltoid contracture may influence rotator cuff function and lead to subsequent tearing. The purpose of this study was to investigate the imaging and clinical factors related to rotator cuff tear in patients with deltoid contracture. METHODS: We retrospectively reviewed 48 shoulders in 44 patients with magnetic resonance imaging diagnosis of deltoid contracture and surgically-proven rotator cuff tear. These shoulders were subdivided into partial-thickness and full-thickness tear groups. Another 17 shoulders in 17 patients with deltoid contracture but no evident rotator cuff tear were included as the control group. The characteristics, including age, gender and imaging features, of these three groups were compared. RESULTS: Two patients who underwent initial operations for cuff tears required secondary operations for distal release of deltoid contracture. The age of patients with full-thickness tear was significantly greater than that of patients with partial-thickness tear or without tear. The winging angle of the glenoid (WAG) in the full-thickness tear group was significantly greater than that in the partial-thickness tear group. Patients with partial-thickness tear also had greater WAG than those without tear. However, WAG was not significantly correlated with the fibrotic size or age of the patient. CONCLUSION: In patients with deltoid contracture, age and WAG are associated with the development of rotator cuff tear. To prevent the occurrence of rotator cuff tear, early surgical release of deltoid contracture is highly recommended, especially in patients with greater WAG.

Adult↗

Initial experience of Integra in the treatment of post-burn anterior cervical neck contracture.

Bilaminate bioartificial skin substitutes such as Integra have been described as a temporary substitute for autograft in acute burns. The aim of this study was to assess their role in the treatment of hypertrophic scarring and anterior neck contracture in the reconstructive phase of burns surgery. Five patients underwent Integra grafting over a 12-month period, with one patient having the procedure performed on two separate occasions. One patient had a combination of hypertrophic scarring of the face and neck contracture, and two patients suffered from recurrent folliculitis in hypertrophic scars in the bearded area of the neck. Mean hospital stay was 24 days (range, 19-30 days). Mean follow-up was 48 months (range, 43-54 months). In all cases of neck contracture a superior cosmetic result was achieved. Recurrence of contracture of greater than 50% occurred within the follow-up period in all cases. Ineffective immobilisation of the graft and overgranulation were identified as contributing to contracture recurrence. Based on our initial experience bilaminate artificial skin substitutes offer an improved cosmetic result in cases of neck contracture and hypertrophic scarring, particularly in the bearded area of the neck. Recurrence of neck contracture remains a problem despite improved techniques of immobilisation. Long-term follow-up will be necessary to assess the applications of this technique fully.

Adult↗

[Scoliosis and hip flexion contracture in Duchenne muscular dystrophy].

UNLABELLED: Spinal deformity is common in muscular dystrophy and usually occurs after loss of walking ability. Unlike in idiopathic and other scoliosis forms, there seems to be no side preference of the convexity. Aim of the study was to analyse, if there is any relation between incidence and extent of walking ability, lower limb contractures and development of scoliosis. METHODS: In a retrospective study, 45 patients with Duchenne muscular dystrophy who underwent surgery were analysed, concerning walking ability, contractures of lower extremities and scoliosis. RESULTS: 1: No scoliosis was observed in ambulatory patients. 2: 96% of the wheelchair bound patients suffered from scoliosis. 3: 96% of the scoliosis patients had hip flexion or abduction contractures. 4: In 12 of 15 cases with side-different contractures, scoliosis tended to the side with the greater contracture. CONCLUSIONS: The influence of hip contracture and pelvic obliquity on scoliosis is discussed controversially. Concerning muscular dystrophy, there seems to be a positive correlation between convexity and hip contracture. If this is a causal relation or if there is a faster progression of structural alteration of the muscles on one side has to be further investigated.

Adolescent↗

[Flexion contractures of the PIP joints: pathogenesis, classification and results following arthrolysis].

The most frequent cause of flexion contracture is immobilization, which may occur with or without trauma. Posttraumatic flexion contracture mainly develops from direct injury, intraarticular fluid and the physiological muscle balance. Nontraumatic post-immobilisation stiffness is due to biochemical and biomechanic changes as well as processes, which are determined by the metabolic activities of tissue and the lack of stress. Because of the variable and the changing anatomical substrates, and owing to different prognostic factors, it is necessary to subdivide the group of flexion contractures with regard to their prognostic factors. Thus, we recommend to differentiate between simple periarticular contractures, complex periarticular contractures with tenodesis and/or contractures caused by scars, as well as a corresponding classification of corresponding treatment procedures. The results in the literature will then be categorized accordingly within a metaanalysis. With regard to the reduction of flexion contractures and the range of motion, the group of simple periarticular arthrolysis shows better results than the group of complex periarticular arthrolysis. The mediolateral approach is preferred in the first group.

Biomechanical Phenomena↗