Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This investigation sought to determine if the Ca2+ antagonist, TMB-8, alters the contracture responses of malignant hyperthermia susceptible (MHS) skeletal muscle to halothane and to caffeine. Muscle fiber bundles were excised from both MHS and normal pigs and exposed to TMB-8 (100 microM), halothane (3%) and caffeine (0.5-8.0 mM), administered alone and in combination. TMB-8 depressed tension developed during isometric twitches in both MHS and normal muscle but had no effect on resting tension (RT). Halothane, however, increased RT in MHS but not in normal muscle. TMB-8 failed to reduce the halothane contracture of MHS muscle but hastened its onset. Caffeine concentrations of greater than or equal to 2 mM increased RT in MHS whereas only 8 mM evoked contracture of normal muscle. These effects were also unaltered by TMB-8. Results suggest that TMB-8 does not inhibit halothane nor caffeine contractures of MHS muscle.
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PMID:Effects of the calcium antagonist, TMB-8 on halothane and on caffeine contractures of malignant hyperthermia susceptible skeletal muscle. 238 62

The realisation and reliability of the halothane-caffeine contracture tests in children to detect the susceptibility to malignant hyperthermia (MH) is still controversial. The present study concerned 26 children aged 2 to 13 years, (mean 9.5 +/- 1.3 years) who were tested either because of a personal symptomatology (14 cases) or as a member of a susceptible MH family (12 cases). Half of the children had a positive test (MHS and MHE) as is found in adults. Furthermore comparison of threshold concentrations of halothane and caffeine as well as the 32 nmol caffeine-induced contractures dit not show significant differences related to age. These results support the possibility to perform under good conditions and with good reliability the diagnostic test of susceptibility to malignant hyperthermia in children from 2 years on.
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PMID:[Diagnosis of susceptibility to malignant hyperthermia in children]. 240 68

Preparing skeletal sarcoplasmic reticulum from both normal and malignant hyperthermia susceptible pigs, the effects of various drugs on the passive calcium permeability of these sarcoplasmic reticulum preparations were studied. It was found that, in the absence of halothane, the permeability of heavy sarcoplasmic reticulum prepared from malignant hyperthermia susceptible pigs was much higher than that of normal pigs. It was observed that halothane, at concentrations above 10 microM (well below anesthetic concentrations, which are on the order of 1 mM), increased the permeability of sarcoplasmic reticulum. The Hill coefficient of the effect of halothane ranged from 1.96 to 2.25, suggesting that some kind of cooperativity was involved in this reaction. The effects of caffeine were similar to those of halothane. Inhibitors, such as tetracaine and ruthenium red inhibited both the calcium permeability and the halothane-induced increment. The Hill coefficient of the effect of tetracaine was 1.75. The mode of inhibition suggests that tetracaine directly binds with the calcium channel to inhibit the calcium efflux. On the contrary, dantrolene did not affect the calcium permeability of the sarcoplasmic reticulum. However, it inhibited the halothane-induced and caffeine-induced increments of the permeability. The Hill coefficient of inhibition by dantrolene ranged from 2.3 to 3.9, suggesting that several molecules of dantrolene may interact cooperatively with one calcium release channel to inhibit the effect of halothane. These results suggest that dantrolene has a unique inhibitory action, which may be related to its efficacy in ameliorating the syndrome of malignant hyperthermia.
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PMID:Effects of halothane, caffeine, dantrolene and tetracaine on the calcium permeability of skeletal sarcoplasmic reticulum of malignant hyperthermic pigs. 243 28

Previous studies in cat, rat, and swine have implicated fiber type as influencing the halothane and caffeine contracture test used to diagnose malignant hyperthermia (MH). The authors performed fiber type analysis using myosin ATPase stains on 31 fascicles of skeletal muscle from nine patients following contracture testing. There was no significant difference in fiber type composition between fascicles from MH negative (n = 5) and MH positive (n = 4) patients. Furthermore, examining each of the 31 fascicles, the authors found no correlation (P greater than .05) of contracture magnitude with percentage of either Type I or Type II fibers using the Pearson Product-Moment correlation calculation. The authors conclude that fiber type composition does not influence contracture test results in human biopsies.
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PMID:No relationship between fiber type and halothane contracture test results in malignant hyperthermia. 244 Mar 53

The ideal screening test for malignant hyperthermia susceptibility (MHS) has yet to be discovered. It should be simple noninvasive, yet totally specific and sensitive. Until such an ideal test becomes available, allowing simple routine preoperative screening, tests should only be used in certain specific situations. These include: patients in whom a clinical crisis was suspected; the members of the family of a subject labeled MHS because of a fatal, or otherwise, crisis, or in whom tests were positive; patients with other pathological conditions which could be linked to malignant hyperthermia (MH) (some myopathies, effort or stress MH, neuroleptic malignant syndrome). The various tests proposed in the literature aim at revealing MHN subjects, using or not a triggering agent, halothane most often. However, detecting these abnormalities sometimes gives greater insight into the physiopathology of MH than in the detection of an individual patient's susceptibility. The tests have been classified as in vivo, electrophysiological, blood, and in vitro muscle biochemical, morphological, and pharmacological tests. The discovery of new tests gives renewed hope: CPK levels, platelet tests, calcium sarcoplasmic reticular reuptake, lymphocyte Quin 2 test, nuclear magnetic resonance spectroscopy. However, experts worldwide agree that the only reference test to this day remains the in vitro halothane caffeine contracture tests. These tests have shown their reliability; they must be performed on muscle strips obtained from surgically removed muscle biopsies, by laboratories used to this technique and who have at their disposal a sufficiently large group of MHS subjects with a clear-cut clinical crisis, as well as controls. The patients must therefore travel to these laboratories. The design of common protocols for European laboratories on one hand, and the North American laboratories on the other, is a good guarantee of the reliability of these tests.
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PMID:[Screening tests for malignant hyperthermia susceptibility]. 256 Jun 12

The neuroleptic malignant syndrome (NMS) is an uncommon but dangerous complication of treatment with neuroleptic drugs. A primary defect in skeletal muscle has been suggested in view of similarities in the clinical presentations of NMS and anaesthetic-induced malignant hyperthermia (MH). The in vitro halothane-caffeine contracture tests are the most reliable method of identifying individuals susceptible to MH. The aim of this study was to define if a relationship exists between NMS and MH susceptibility. Hence, the in vitro halothane and caffeine contracture tests were performed on muscle tissue obtained from eight NMS, ten MH-susceptible and ten control patients. The results, which are expressed in accordance with the criteria of the European MH Group, defined the eight NMS subjects as MH non-susceptible. The response to halothane and caffeine exposure of skeletal muscle from NMS and control subjects was the same and significantly different from that of muscle from patients susceptible to MH. Furthermore, muscle from subjects in NMS and control group responded similarly to increasing concentrations of chlorpromazine. These results do not point towards an association between NMS and MH.
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PMID:The association between the neuroleptic malignant syndrome and malignant hyperthermia. 224 51

Signs of malignant hyperthermia, including progressive increases in PaCO2, skin temperature and heart rate, and elevated serum levels of potassium, inorganic phosphate, and creatine kinase, were identified in a halothane-anesthetized horse. Treatment was discontinuing halothane administration, applying ice and cold fluids, and hyperventilating with 100% oxygen. After an initial recovery, bilateral hindlimb myopathy and pigmenturia developed. The myopathy resolved after treatment with oral dantrolene, IV fluids, and hydrocortisone. Results of caffeine-halothane challenge, using semimembranosus muscle collected 2 weeks after the episode, were considered within normal limits for horses. The intraoperative abnormalities were evidently predictive of postanesthetic myopathy but the cause in this horse remained unclear.
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PMID:Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. 260 79

1. Diltiazem (10 mumol/L) and verapamil (10 mumol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures. 2. Like the skeletal muscle relaxant dantrolene sodium (6 mumol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine. 3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive. 4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome. 5. These results also suggest an abnormality in transverse tubule-sarcoplasmic reticulum communication.
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PMID:Effect of diltiazem, verapamil and dantrolene on the contractility of isolated malignant hyperpyrexia-susceptible human skeletal muscle. 261 62

A case of malignant hyperthermia is reported. The clinical symptoms arised after anesthesia and the post-operative enzymatic alterations prompted the Authors to send the patient to the University of Padua where muscle byopsy and caffeine contracture test were performed. The initial diagnosis was confirmed.
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PMID:[Malignant hyperthermia. A case with minimal manifestations]. 261 98

Since ketamine has been incriminated as triggering malignant hyperthermia (MH) [3, 9, 13, 14, 18], but has still been used uneventfully in MH susceptible patients, we performed an in vitro study to examine the safety of ketamine for use in human MH. METHODS. Muscle specimens of 20 patients who had muscle biopsies to diagnose MH were investigated. In every patient diagnostic contracture tests (2 halothane (Hal) and 2 caffeine (Caf) were done according to the protocol established by the European MH group (EMHG). In addition, one test unit for investigating the effect of stepwise increased bath-concentrations of ketamine (5, 10, 20, 60, 120, 240 and 960 mumol/l) and a further one serving as control (no drugs added to the bath) were used. Combined Hal (2 vol%) and Ket (960 mumol/l) tests were performed in 9 patients (4 MHS, 4 MHN, 1 MHEh). Changes in baseline contractures and mechanical twitch tension were evaluated. RESULTS. The diagnostic test showed MHS in 8, MHN in 8 and MHEh in 4 patients. Ketamine did not induce baseline contractures in any of the tests performed. Contractures induced by 2 vol% of halothane in 4 MHS muscles did not change significantly when ketamine was added to the bath (concentration 960 mumol/l). A significant, dose-related decrease in mechanical twitch tension occurred, when ketamine was added to the test. At the highest concentration (960 mumol) twitch tension was reduced by 55%. Twitch tension remained stable in untreated muscles. No significant differences were found between the specimens from MHS, MHN and MHE patients. This reduction in twitch tension was more pronounced in specimens exposed to both halothane (2 vol%) and ketamine (960 mumol/l), resulting in an average decrease of 71%. CONCLUSION. In accordance with Fletcher et al., our results indicate that ketamine - at least in vitro - does not trigger MH. In MHS muscles, ketamine does not augment halothane-induced baseline contractures. The ketamine-induced reduction of mechanical twitch tension in directly stimulated human muscles has not been described before. Analogous findings in frog sartorius muscles can be found in the literature. Whereas the effect of ketamine on indirectly stimulated muscle has been investigated by several authors, the underlying mechanism of ketamine-induced twitch suppression in directly stimulated muscles is not known. Inhibition of calcium release from or accelerated uptake into the sarcoplasmatic reticulum have been reported.
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PMID:[The action of ketamine on muscle contractile behavior. In vitro studies on the musculature of subjects susceptible to malignant hyperthermia]. 261 30


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