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PubMed1989

Block of contracture in skinned frog skeletal muscle fibers by calcium antagonists.

The ability of a number of calcium antagonistic drugs including nitrendipine, D600, and D890 to block contractures in single skinned (sarcolemma removed) muscle fibers of the frog Rana pipiens has been characterized. Contractures were initiated by ionic substitution, which is thought to depolarize resealed transverse tubules in this preparation. Depolarization of the transverse tubules is the physiological trigger for the release of calcium ion from the sarcoplasmic reticulum and thus of contractile protein activation. Since the transverse tubular membrane potential cannot be measured in this preparation, tension development is used as a measure of activation. Once stimulated, fibers become inactivated and do not respond to a second stimulus unless allowed to recover or reprime (Fill and Best, 1988). Fibers exposed to calcium antagonists while fully inactivated do not recover from inactivation (became blocked or paralyzed). The extent of drug-induced block was quantified by comparing the height of individual contractures. Reprimed fibers were significantly less sensitive to block by both nitrendipine (10 degrees C) and D600 (10 and 22 degrees C) than were inactivated fibers. Addition of D600 to fibers recovering from inactivation stopped further recovery, confirming preferential interaction of the drug with the inactivated state. A concerted model that assumed coupled transitions of independent drug-binding sites from the reprimed to the inactivated state adequately described the data obtained from reprimed fibers. Photoreversal of drug action left fibers inactivated even though the drug was initially added to fibers in the reprimed state. This result is consistent with the prediction from the model. The estimated KI for D600 (at 10 degrees and 22 degrees C) and for D890 (at 10 degrees C) was approximately 10 microM. The estimated KI for nitrendipine paralysis of inactivated fibers at 10 degrees C was 16 nM. The sensitivity of reprimed fibers to paralysis by D600 and D890 was similar. However, inactivated fibers were significantly less sensitive to the membrane-impermeant derivative (D890) than to the permeant species (D600), which suggests a change in the drug-binding site or its environment during the inactivation process. The enantomeric dihydropyridines (+) and (-) 202-791, reported to be calcium channel agonists and antagonists, respectively, both caused paralysis, which suggests that blockade of a transverse tubular membrane calcium flux is not the mechanism responsible for antagonist-induced paralysis. The data support a model of excitation-contraction coupling involving transverse tubular proteins that bind calcium antagonists.

Animals↗
PubMed1979

A screening test for the malignant hyperpyrexia phenotype using suxamethonium-induced contracture of muscle treated with caffeine and its inhibition by dantrolene.

Suxamethonium induced a contracture in caffeine pretreated human muscle in vitro. The contracture was significantly greater (P less than 0.001) with MHS muscle compared with muscle from normal subjects. This reaction is now used as an additional screening test for the MHS phenotype. The contracture was prevented by pretreatment with dantrolene.

Adolescent↗
PubMed1991

Ryanodine contracture: a potentially specific in vitro diagnostic test for malignant hyperthermia.

In vitro contracture tests used currently for malignant hyperthermia (MH) do not possess absolute specificity. This is potentially a great problem in the study of the genetic approach which offers the best prospect for the development of a non-invasive diagnostic test for the condition. The calcium release channel of the sarcoplasmic reticulum has been proposed as the site of the MH defect. Ryanodine, which binds avidly to this channel, was shown to differentiate between muscle of MH susceptible and normal patients in terms of in vitro contracture response. This ryanodine contracture response is proposed as a potentially specific in vitro diagnostic test for MH.

Culture Techniques↗
PubMed1992

In vitro diagnosis of malignant hyperthermia: influence of electrical stimulation on the contracture response to caffeine.

We have examined the influence of electrical stimulation on caffeine-induced tension generation during contracture testing used to diagnose malignant hyperthermia. The cumulative contracture response to caffeine was compared in pairs of morphologically comparable muscle bundles obtained from the same patient. Only one of the two bundles was stimulated electrically during the test. Statistically significant differences in tension were found at caffeine concentrations greater than or equal to 4 mmol litre-1, the tension developed being invariably larger in the unstimulated fascicles. These results suggest that electrical stimulation results in suppression of the dose-dependent, caffeine-induced contracture. This effect could be a result of the potentiation of twitch tension by caffeine, muscle fatigue, or both. Overall, the observed differences did not alter the in vitro diagnosis of malignant hyperthermia.

Caffeine↗
PubMed1993

Comparison of in vitro contracture testing with ryanodine, halothane and caffeine in malignant hyperthermia and other neuromuscular disorders.

In vitro exposure of living skeletal muscle to ryanodine has been proposed as a potentially specific test for malignant hyperthermia (MH). In this study we have compared in vitro contracture responses to halothane, caffeine and ryanodine in skeletal muscle specimens obtained from 155 patients attending for diagnosis of susceptibility of MH and also from six patients having muscle biopsy for diagnosis of other neuromuscular disorders. Although the ryanodine contracture test was not specific for MH, the results suggest it may greatly aid (in conjunction with the standard halothane and caffeine contracture tests) the accurate phenotyping of individuals that is essential for the further genetic analysis of MH.

Caffeine↗
PubMed1993

Effects of inhibition of transsarcolemmal calcium influx by nickel on force of postrest contraction and on contracture induced by rapid cooling.

OBJECTIVE: The aim was to characterise the influence of a decrease in transsarcolemmal calcium influx on the calcium content of the sarcoplasmic reticulum and on the force of postrest contraction, which is largely activated by calcium released from the sarcoplasmic reticulum. METHODS: Isometric force of postrest contractions in isolated rabbit papillary muscles was measured in the absence and in the presence of ryanodine (1 microM). The force measured in the presence of ryanodine was used as an index of transsarcolemmal calcium influx. The calcium content of the sarcoplasmic reticulum was estimated by rapid cooling induced contracture measurements. Nickel (Ni2+) was used to decrease the calcium influx, and the results were compared to those obtained by lowering the extracellular calcium concentration. RESULTS: The addition of Ni2+ or lowering extracellular Ca2+ markedly decreased the force of postrest contraction measured in the presence of ryanodine, and moderately decreased the force of postrest contraction measured in the absence of ryanodine. Neither the addition of Ni2+ nor lowering extracellular Ca2+ decreased maximum rapid cooling induced contracture; this was actually increased in the presence of Ni2+ even though a larger number of stimuli was required in the presence than in the absence of Ni2+ for the force of the subsequently elicited contracture to reach the maximum level. CONCLUSIONS: The results suggest: (1) that a decrease in the calcium influx reduces the force of the postrest contraction by decreasing the amount of calcium required to trigger the release of calcium from the sarcoplasmic reticulum, without decreasing its maximum calcium content; and (2) that Ni2+ decreases the rate of filling of sarcoplasmic reticular calcium stores even though the calcium content of the sarcoplasmic reticulum after a sufficiently large number of beats is higher in the presence of Ni2+ than in its absence.

Animals↗
PubMed1983

Diltiazem and nitrendipine suppress hypoxic contracture in quiescent ventricular myocardium.

Calcium blocking agents may protect the ischaemic heart by reducing ventricular afterload and cardiac contractility, or by augmenting myocardial perfusion. To determine whether protection is mediated in part by mechanisms unrelated to myocardial work and perfusion, we examined effects of diltiazem and nitrendipine on unperfused myocardium subjected to hypoxia. Rabbit right ventricular papillary muscles were mounted in a myograph containing Krebs buffer equilibrated at 37 degrees C with 95% O2-5% CO2. During brief electrical pacing at a frequency of 12 min-1, a preload of 1363 +/- 60 mg produced a maximal isometric force development of 4892 +/- 273 mg (SE; n = 113). After 60 min without pacing, the quiescent muscles were pre-equilibrated randomly for 20 min without drug for control (C = 38), or with 10(-6) diltiazem (n = 38) or 10(-6) mol l-1 nitrendipine (n = 38). Changes in resting force during equilibration did not exceed +/- 12 mg. Subsequent sudden de-oxygenation with 95% N2-5% CO2 evoked in controls an increase in force beginning after 16 +/- 1 min. The onset of hypoxic contracture was significantly (P less than 0.1) delayed in treated muscles and started after 31 +/- 3 min with diltiazem and after 23 +/- 2 min with nifedipine. Peak contracture was significantly (P less than 0.1) inhibited by diltiazem and nitrendipine compared to controls, respectively values averaging 264 +/- 22 mg, 480 +/- 44 mg and 895 +/- 70 mg. Thus, calcium blockers delayed and suppressed hypoxic contracture in quiescent myocardium, demonstrating that the drugs acted directly on cardiac muscle in the absence of rhythmic electrical and mechanical activity.

Animals↗
PubMed1996

Comparison of the segregation of the RYR1 C1840T mutation with segregation of the caffeine/halothane contracture test results for malignant hyperthermia susceptibility in a large Manitoba Mennonite family.

BACKGROUND: Malignant hyperthermia (MH) is an important cause of anesthesia-induced death. Malignant hyperthermia susceptibility is diagnosed using the in vitro caffeine/halothane contracture test (CHCT) in fresh muscle biopsy specimens. The CHCT test is highly invasive, expensive, and lacks 100% specificity. Genetic and biochemical evidence provide strong support for the view that the substitution of cysteine for arginine 614 (Arg614Cys) in the human ryanodine receptor gene is one of several mutations that are likely to cause human MH. DNA testing was compared with CHCT as a means of predicting MH susceptibility in a large MH family in which the Arg614Cys mutation was detected. METHODS: A comparison of CHCT and DNA-based diagnosis was conducted in a large Manitoba Mennonite MH kindred identified by an index patient who died at age 45 yr of an MH crisis after general anesthesia. The presence of the Arg614Cys mutation was detected through a combination of polymerase chain reaction and restriction endonuclease digestion. Blood samples for DNA analysis were obtained from 68 family members, including 19 who had undergone muscle biopsies and 1 who had a documented crisis but did not undergo biopsy. Family members were classified as MH-susceptible or MH-normal on the basis of the CHCT. RESULTS: Twenty-two persons were found to be heterozygous for the Arg614Cys mutation. Five of these persons had prior positive CHCT results and one had an MH crisis but did not undergo biopsy. On DNA testing, 44 persons were found to be homozygous for the normal allele. Of these, ten had been classified as MH-normal and five as MH-susceptible on the basis of the CHCT. On reevaluation of the data obtained in our earlier CHCT diagnoses, we found that the condition of the muscle was poor, with no twitch, for three of five individuals homozygous for the normal allele but originally classified as MH-susceptible and for one who was homozygous for the normal allele and originally classified as MH-normal. Caffeine/halothane contracture test results for these four persons were considered invalid. The twitch response was good for the two remaining persons who were homozygous for the normal allele but classified as MH- susceptible, because contracture was observed with appropriately low levels of both caffeine and halothane. CONCLUSIONS: An absolute correlation between DNA test results and CHCT assignment could not be made in this kindred. Possible explanations for discordance are that the Arg614Cys mutation is not linked to MH, that a second MH mutation is segregating in the family, or that there are errors in the CHCT. Because there is strong evidence supporting the causal nature of the Arg614Cys mutation, the discordant persons are not closely related within the pedigree as they would be if a second MH mutation were segregating, and the CHCT is not 100% accurate, we propose that the observed discordance between DNA test results and CHCT assignment in this kindred results from two false-positive diagnoses by the CHCT.

Anesthetics, Inhalation↗
PubMed1987

Vitamin E and capsule contracture.

Vitamin E is known to inhibit the inflammatory phase of wound healing and to decrease wound tensile strength. For these reasons, vitamin E has been suggested for the prevention of breast implant capsule contracture. Experiments in rabbits demonstrated a reduction in capsule contracture that was significant statistically, but the improvement was minor, suggesting that vitamin E prophylaxis would probably not have a major impact on the clinical problem of capsule contracture.

Animals↗
PubMedDate not supplied

Distal femoral extension osteotomy for knee flexion contracture in patients with arthrogryposis.

Severe knee flexion contractures in patients with arthrogryposis multiplex congenita were treated by distal femoral extension osteotomy. Thirty-two operations were followed for an average of 32 months. Contractures were corrected from 49 degrees to 6 degrees. During follow-up there was a loss of correction of 22 degrees at a rate of 0.9 degrees/ month. The angle of the distal femoral physis and the shaft of the femur was 2 degrees of flexion preoperatively, and postoperatively it measured 43 degrees of extension and at late follow-up it measured 19 degrees. Remodeling occurred at a rate of 1.0 degrees/month, which correlated with recurrence. All patients increased their ambulatory ability at least one level. There was one wound infection. Distal femoral extension osteotomy is effective and safe for the correction of knee flexion contracture. Recurrence occurs in all growing children.

Adolescent↗
PubMed1978

Influence of some operative and postoperative factors on capsular contracture around breast prostheses.

In a follow-up of 490 patients with breast implants, neither the size of the prosthesis nor the nature of the surgical procedure (simple augmentation mammaplasty or after subcutaneous mastectomy) increased the incidence of capsular contracture. Hematoma or infection were followed by a higher incidence of capsular contracture. Drainage with suction and the instillation of steroid around the prostheses seemed to be effective in reducing the incidence of capsular contracture. In the steroid-treated group, the need for open surgical treatment was reduced. The recurrence rate after closed capsulotomy, or open capsulotomy, was not significantly different from that following the more extensive procedure of capsulectomy.

Breast↗
PubMedDate not supplied

Postburn subtalar dislocation in a major foot contracture.

An unusual postburn contracture, which consists of calcaneal bone dislocation and severe dorsiflexion contracture of foot and toes, is presented. To our knowledge, subtalar dislocation as the result of postburn contracture has not been previously reported in the literature.

Adolescent↗
PubMed2006

A technique for correction of equinus contracture using a wire fixator and elastic tension.

Equinus contracture often is a complication of trauma, burns, or neurologic deficit. Many patients with contractures secondary to trauma or burns have poor soft tissue, which makes invasive correction a less appealing option. The Ilizarov external fixator has been used as a less invasive attempt to correct equinus contracture. We describe our "dynamic" technique and present a clinical patient series using a variation of the unconstrained Ilizarov technique, which uses elastic bands rather than threaded rods to supply the corrective force.

Adult↗
PubMed2005

Anastomotic contracture and incontinence after radical prostatectomy: a graded approach to management.

PURPOSE: We present a heterogeneous group of men presenting with varying degrees of anastomotic contracture (AC) and associated stress urinary incontinence (SUI) following radical prostatectomy. It is particularly important that AC should be resolved before artificial urinary sphincter (AUS) implantation, because instrumentation through the AUS can risk erosion. MATERIALS AND METHODS: The records of 54 consecutive men who were referred for the management of AC and associated SUI were reviewed. Patient treatment and outcomes were stratified according to their unique characteristics. RESULTS: A total of 54 patients underwent radical prostatectomy alone (48), or in combination with radiation therapy (7) or cryotherapy (1). In group 1, 35 patients had previously undiscovered AC, or 1 or more prior contracture incisions (CIs) with SUI. CI and AUS were performed simultaneously in 33 patients and sequentially in 2. In group 2, 7 patients with intractable AC following multiple CIs/dilations and self-calibration, or an indwelling urethral or suprapubic catheter underwent simultaneous (3) or sequential (2) CI/AUS or CI only (2). Five patients required temporary self-calibration. In group 3, in 12 patients with total outlet obliteration recanalization was accomplished with combined antegrade/retrograde endoscopy and CI. Ten patients had re-obliteration, of whom 1 underwent suprapubic diversion and 9 underwent repeat recanalization with placement of a UroLume stent (American Medical Systems, Minnetonka, Minnesota) across the anastomosis. Eight patients underwent artificial urinary sphincter (AUS) placement 4 to 6 weeks later and 1 awaits an AUS. Of those implanted with an AUS 2 required repeat endoscopic procedures because of recurrent but manageable stent ingrowth. CONCLUSIONS: Most ACs are treated successfully with simultaneous, aggressive CI/AUS. A history of many CIs or long, dense contractures suggest the need for staged management. In those with obliterated outlets we prefer to reestablish patency and if rapid recurrence develops, we place a UroLume stent. Regardless of a history of radiation therapy, continence is restored with an AUS.

Anastomosis, Surgical↗
PubMed1997

Multiple congenital contractures.

A cross-sectional study of 28 patients with multiple congenital contractures of miscellaneous origin is presented. We describe the clinical, genetic, and neurological diagnosis and the involvement of upper and lower extremities and spine. All treatments that patients received so far as well as functional outcome were studied. We compared these factors in children with anterior horn cell degeneration (AHCD) or amyoplasia with those of children with contractures of other origin. A correct genetical diagnosis of multiple congenital contracture is important because children with AHCD will need more extensive treatment than others, and their functional outcome seems to be worse.

Abnormalities, Multiple↗
PubMed2026

A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy.

Lethal congenital contracture syndrome 3 (LCCS3, MIM #611369) is a rare autosomal recessive neuromuscular disorder caused by biallelic loss-of-function (LOF) variants in PIP5K1C, reported in only two families to date. It typically presents with severe fetal akinesia, arthrogryposis multiplex congenita, and perinatal lethality due to respiratory insufficiency case. Herein, we report a new case with survival beyond birth. Prenatal findings included clubfeet with preserved amniotic fluid volume and fetal movements. The infant was delivered by cesarean section at 37 + 7 weeks following breech presentation and developed respiratory distress requiring 14 days of ventilatory support. Physical examination revealed bilateral talipes equinovarus, flexion contractures of the knees, restricted hip mobility, clenched hands with flexion contractures of the third and fourth fingers, and hyperextension of the second and fifth fingers. Neurologically, he had encephalopathy, profound hypotonia with a frog posture, and abnormal neonatal reflexes with a discontinuous background pattern on cerebral function monitoring. Additional observed features were bilateral optic atrophy and hyperinsulinemic hypoglycemia responsive to Diazoxide. Trio genome sequencing identified a homozygous pathogenic splice-site variant in PIP5K1C (c.1127+1G>A, NM_012398.3). The infant died at 6 months from multisystemic failure. Further studies are warranted to elucidate the pathomechanisms underlying the PIP5K1C defect and its phenotypic consequences.

LCCS3↗
PubMed1991

The caffeine contracture test for malignant hyperthermia: caffeine citrate, caffeine benzoate or caffeine free base?

The aim of the present study was to investigate whether the three different caffeine preparations--caffeine citrate, caffeine benzoate and the free base--used for in vitro diagnosis of malignant hyperthermia susceptibility--produced the same amount of contracture in rat diaphragm. At equimolar caffeine concentrations, the pure base generated more tension in the rat diaphragm muscle than caffeine benzoate or caffeine citrate. The citrate lowers the pH and the free Ca2+ concentration of the test bath and thus suppresses the caffeine contracture. The benzoate is believed to inhibit the caffeine contracture by its carbonyl group in a way similar to the effect of benzocaine.

Animals↗
PubMed1992

Effect of halothane equilibration kinetics on in vitro muscle contractures for malignant hyperthermia screening.

In vitro muscle contracture tests for malignant hyperthermia screening are routinely performed using standardized protocols. In the present study on-line monitoring of halothane concentrations in the gas phase was demonstrated to be an improved test standard. The kinetics of halothane concentration and their effect on in vitro muscle contracture tests were evaluated in two test baths, I and II, which contained 3 and 18 ml Krebs-Ringer solution, respectively. The equilibration kinetics for halothane was significantly faster in bath I (t1/2 = 8.2 s) compared with bath II (t1/2 = 25.6 s). Twenty-one pairs of muscle bundles from 21 potentially malignant hyperthermia susceptible patients were investigated, each test bath receiving one bundle from each pair. The variance of muscle contractures was significantly increased in test bath I compared with test bath II. However, there was no influence on malignant hyperthermia diagnosis, suggesting that, within the ranges of t1/2 = 8.2 s-25.6 s, the test bath volumes need not be standardized.

Disease Susceptibility↗