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)

Two 2-year-old males underwent muscle biopsy that established the histopathologic diagnosis of Becker dystrophy in one, and Duchenne dystrophy in the other. Concomitant contracture testing with caffeine or halothane was normal for malignant hyperthermia (MH). The results suggest that acute hypermetabolism or acute rhabdomyolysis during anesthesia, in patients with these disorders, is related to the X-linked myopathy and its associated muscle deterioration, rather than to the autosomal dominant MH.
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PMID:Absence of malignant hyperthermia contractures in Becker-Duchenne dystrophy at age 2. 173 62

In 22 patients susceptible to and 34 patients not susceptible to malignant hyperthermia, we examined which muscle conditions may influence the degree of sensitivity of skeletal muscle to the in vitro caffeine contracture test: predrug resting membrane potential, predrug twitch tension, and maximum contracture induced by 32 mM caffeine in two caffeine tests performed respectively at 30 and 75 min after biopsy. No differences in the measured variables were observed between the first and the second caffeine tests in the 34 patients susceptible to malignant hyperthermia. The first caffeine test was found to be positive in all of the 22 patients susceptible to malignant hyperthermia. However, in eight patients, the second caffeine test was negative and the muscle fibers were found to be significantly depolarized. Resting membrane potential was -73.4 +/- 7.9 mV before the first caffeine test and -65.8 +/- 8.8 mV before the second test. We suggest that when time-induced partial depolarization of malignant hyperthermia-susceptible fibers occurs, fibers may become less sensitive to caffeine.
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PMID:Is resting membrane potential a possible indicator of viability of muscle bundles used in the in vitro caffeine contracture test? 173 69

In order to investigate the relationship between neuromuscular disease and malignant hyperthermia (MH) susceptibility, the caffeine and halothane in vitro contracture test (European Malignant Hyperthermia Group Protocol) were performed in 60 patients who underwent muscle biopsy for investigation of a clinically suspected neuromuscular disorder. Two test results were classified as MH susceptible, 10 as MH equivocal and 48 MH negative. The large number of equivocal results is thought to indicate the lack of specificity of the individual components of this test in patients with clinical or histological evidence of neuromuscular disease. The increased in vitro sensitivity to the drugs tested may nevertheless provide some explanation for several in vivo "MH-like reactions" reported frequently in these patients. These reactions, however, are likely to be based on pathophysiological mechanisms different from those responsible for a true MH crisis.
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PMID:In vitro contracture tests in patients with various neuromuscular diseases. 173 72

The effects of commonly used intravenous anaesthetic agents ketamine, thiopental sodium and propofol on the caffeine-alone or halothane-plus-caffeine-induced muscle contractures were investigated to determine safety for use in patients susceptible to malignant hyperthermia (MH). The muscle strips from rat diaphragm were exposed to one of these anaesthetic agents prior to challenge with caffeine 8 mmol/l alone or halothane 3% plus caffeine 8 mmol/l together. None of the three agents induced contractures when added alone. Ketamine 100 mumol/l and thiopental sodium 300 mumol/l augmented neither caffeine-alone nor caffeine-with-halothane contractures significantly and these two agents appear to be safe for use in MH-susceptible patients. In contrast, propofol 150 mumol/l augmented these contractile responses significantly and may not be recommended for use in patients known to be susceptible to this anaesthetic complication.
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PMID:Effects of ketamine, thiopental sodium and propofol on muscle contractures in rat diaphragm in vitro. 174 5

Malignant hyperthermia (MH) is an adverse reaction most frequently associated with the administration of halogenated inhalational anesthetic agents and the depolarizing muscle relaxant succinylcholine. Characteristic findings are a hypermetabolic state accompanied by extreme hyperpyrexia, acidosis, rhabdomyolysis, and generalized muscle rigidity, often involving the masseter muscles. Dantrolene sodium, which was approved in 1979 by the FDA for use in the prevention of MH in high-risk patients, has neurologic and gastrointestinal side effects. At the Children's National Medical Center (CNMC), 24 children identified as being at risk for the development of a MH reaction were anesthetized for otolaryngic procedures by using "non-triggering" anesthetics and without use of dantrolene sodium. These patients represent 56% of all patients at risk for MH or masseter muscle rigidity (MMR) reactions during an 8-year period at the CNMC. There were no complications. Concomitant muscle biopsies were performed, and caffeine/halothane contracture studies were completed in 18 of these patients, demonstrating 11 susceptible or equivocal responses. The data suggest that children undergoing common otolaryngic procedures who are at risk for development of MH may be safely anesthetized without the use of prophylactic dantrolene sodium.
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PMID:Management of otolaryngic patients susceptible to malignant hyperthermia without dantrolene. 175 51

We have studied the question of the possible role of sarcoplasmic reticulum (SR) in the interaction of volatile anesthetics (such as halothane, enflurane and isoflurane) with muscle. We used two cardiac muscle models, i.e., isolated rat myocytes and Langendorff perfused rat hearts. We compared the results with those for skeletal muscle SR from rabbits, rats and pigs susceptible to malignant hyperthermia (MH). In both skeletal and cardiac muscle SR, volatile anesthetics enhanced the calcium release from the SR. In cardiac muscle, these agents are known to decrease contractility (negative inotropism). We found that caffeine, a well-known agent which releases calcium from the SR, also had a negative inotropic effect in cardiac muscle, raising the possibility of an unexpected link between the potentiation of calcium release and mechanism underlying the observed negative inotropism. Current understanding of anesthetic mechanisms does not include this possibility. We further found that both volatile anesthetics and caffeine decrease the content of calcium in the SR, suggesting that the increase of calcium permeability results in the decrease of calcium ions in the SR which are available for excitation-contraction (E-C) coupling. In MH-susceptible skeletal muscle, a similar increase in calcium permeability does not cause a decrease of contractility, but rather may contribute to a fatal syndrome of temperature increase provoked by abnormal contracture. This difference may be because in skeletal myoplasm calcium ions recycle internally, while in the cardiac muscle cell they are in dynamic equilibrium with extracellular calcium ions.
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PMID:Why does halothane relax cardiac muscle but contract malignant hyperthermic skeletal muscle? 176 5

The halothane-caffeine contracture test is presently the most well-established method for identification of malignant hyperthermia susceptibility (MHS) or non-susceptibility (MHN). However, 10-20% of the patients tested are classified as equivocal (MHE), i.e. their susceptibility remains uncertain. A genetic disorder of the calcium releasing ryanodine receptor has been postulated recently. Therefore, 12 patients were tested in addition to the protocol of the European Malignant Hyperthermia Group (EMHG) for dose- and time-dependent contracture after ryanodine application. In this study, contracture of 0.2g appeared significantly earlier in MHS patients (17.5 +/- 1.7 min; n = 5) during cumulative ryanodine exposition (0.4-0.8-1.6-10.0 mumol/l) than in MHN (38.2 +/- 5.4 min; n = 5). A significant difference between MHS (10.0 +/- 1.7 min; n = 6) and MHN (19.8 +/- 0.6 min; n = 3) was also seen after bolus application of ryanodine (10.0 mumol/l). One patient classified as MHE according to the EMHG protocol, manifested as MHN after the ryanodine contracture test. This study supports previous work suggesting the ryanodine contracture test as an improvement in the in-vitro diagnosis of MH susceptibility.
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PMID:[Ryanodine-induced contractures for the diagnosis of malignant hyperthermia susceptibility]. 178 6

An eight-year-old boy was scheduled for an orthopaedic operation with a clinically abortive reaction of malignant hyperthermia and a positive platelet test result. Since there has been no validation for this platelet test, we performed a muscle biopsy and the caffeine- halothane-contracture test (CHCT). The young patient was found to be negative (MHN) in CHCT. Furthermore, the valence and the validity of the used platelet test are discussed for diagnostic purposes. With regard to resulting consequences, first of all in respect of possibly false negative results, we suggest to investigate all patients classified by this platelet test with the accepted and established CHCT.
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PMID:[Diagnosis of malignant hyperthermia. The platelet test versus the in vitro contracture test]. 178 9

Malignant hyperthermia syndrome (MHS) is rare, inherited, and triggered by volatile anesthetics and depolarizing muscle relaxants. While potentially fatal, if recognized and treated early recovery is usual. However, the condition is often not recognized until an extreme increase in temperature develops with profound circulatory depression. In this stage the syndrome is irreversible, despite specific treatment with dantrolene. At present, the only reliable diagnostic test for susceptibility to malignant hyperthermia requires sampling of viable muscle for in vitro contracture tests with caffeine and halothane. Until our malignant hyperthermia diagnostic center was opened, such tests could not be performed in Israel. Since then we encountered a 22-year-old man who developed the partial picture of malignant hyperthermia syndrome during anesthesia for inguinal herniorrhaphy. He received dantrolene and recovered. 4 months later in vitro contracture tests with caffeine and halothane performed on biopsied muscle confirmed the diagnosis.
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PMID:[In vitro diagnosis of malignant hyperpyrexia syndrome]. 179 53

1. Azumolene sodium is a new water-soluble derivative of dantrolene sodium that also acts as a skeletal-muscle relaxant. 2. Azumolene (6 mumol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)-susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses. 3. Like dantrolene, azumolene (6 mumol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations. 4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine-induced contractures, and the converse was also true. This was observed in both MH-susceptible and control preparations. 5. Sarcoplasmic reticulum Ca(2+)-dependent ATPase activity from MH-susceptible and control muscle was not affected by azumolene. 6. Like dantrolene, azumolene may inhibit Ca2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.
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PMID:The effect of azumolene on hypercontractility and sarcoplasmic reticulum Ca(2+)-dependent ATPase activity of malignant hyperpyrexia-susceptible porcine skeletal muscle. 183 2


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