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)

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.
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PMID:Malignant hyperthermia in dogs. 203 26

Malignant hyperthermia is a potentially fatal pharmacogenetic disorder triggered by volatile anesthetics (halothane, enflurane, isoflurane) and/or succinylcholine. The inheritance of malignant hyperthermia susceptibility is thought to be autosomal dominant and the incidence could be as high as 1:10,000. The only generally accepted diagnostic method at present involves a muscle biopsy followed by in-vitro halothane and caffeine contracture tests. 100 individuals from 45 families who were considered to be potentially malignant hyperthermia-susceptible were investigated from 1986 to 1990 by in-vitro muscle contracture tests using the protocol of the European Malignant Hyperthermia Group. Of 45 families analyzed, 28 had at least one person who was susceptible to malignant hyperthermia with a total of 64 malignant hyperthermia-susceptible individuals. 36 subjects in the 45 families were normal. In addition, our study shows that a femoral nerve block can be used in outpatients as a reliable anesthetic technique to perform biopsies from the vastus medialis muscle for malignant hyperthermia screening.
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PMID:[Diagnosis of susceptibility for malignant hyperthermia using in-vitro muscle contraction testing in Switzerland]. 204 40

Malignant hyperthermia (MH) is currently diagnosed by the caffeine-halothane contracture (CHC) test. In a previous study, this test was used to establish linkage between the human gene for MH susceptibility and the ryanodine receptor (RYR) gene. The current study extends the genetic linkage analysis to a large French-Canadian kindred. In this family, genetic linkage between RYR and MH genes was not demonstrable using the currently recommended limits of normal for the CHC test in the identification of MH-susceptible individuals. With CHC test threshold limits below those currently recommended, however, complete linkage between the RYR and MH genes was seen. Comparisons of CHC test results with genetic linkage studies will increase the diagnostic accuracy of both tests as well as generate new insights into the biology of MH.
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PMID:A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia. 206 33

The role of succinylcholine in the precipitation of malignant hyperthermia (MH) necessitates the testing of new neuromuscular relaxants for their ability to trigger MH in MH-susceptible swine before general human use. We tested doxacurium and mivacurium, two new nondepolarizing bis-benzylisoquinolinium neuromuscular relaxants, at ED95 and at four times ED95 doses in swine previously documented to be MH-susceptible. In none of the 16 animals was MH triggered after administration of these relaxants, whereas all animals developed fatal MH after administration of halothane or halothane plus succinylcholine. Muscle biopsy specimens taken before administration of the relaxant confirmed that all animals had increased sensitivity to halothane, caffeine, or both. Thus, we conclude that doxacurium and mivacurium are not triggering agents of malignant hyperthermia in MH-susceptible swine.
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PMID:Doxacurium and mivacurium do not trigger malignant hyperthermia in susceptible swine. 214

Malignant hyperthermia (MH) is a hypermetabolic and hypercontractile syndrome triggered by anesthesia or various stressors that cause a sustained increase in sarcoplasmic ionized Ca. Susceptibility is apparently inherited in an autosomal dominant pattern. The primary molecular defect results in hypersensitive ligand-gating of the Ca-release channel of sarcoplasmic reticulum (SR) in skeletal muscle: channel opening is stimulated by abnormally low concentrations of agonist. We attribute MH to a mutation in the gene for the fast twitch muscle isoform of the Ca-channel, resulting in the expression of a cardiac-like isoform in fast muscle. Syndromes with some resemblance to MH can occur due to other genetic or acquired imbalances in Ca-flux across SR that favor net release of Ca. Either defective uptake or release can be detected as increased sensitivity of muscle to the contracture-producing effects of caffeine and halothane. Thus, caffeine and/or halothane contracture tests for MH-susceptibility may give false positives when there is decreased Ca-uptake, such as in muscular dystrophies. Ca-channel hypersensitivity and decreased Ca-uptake activity can be detected by assays using isolated SR. Functional assays using lymphocytes are being assessed as potential replacements for muscle contracture tests. Polymorphism analysis of proteins or nucleic acids for the MH or closely-linked genes has been used to trace the inheritance of MH-susceptibility.
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PMID:Malignant hyperthermia susceptibility: biochemical basis for pathogenesis and diagnosis. 215 50

A crude preparation of heavy sarcoplasmic reticulum (HSR) was isolated using 1 gram of muscle obtained from swine susceptible to malignant hyperthermia (MH) and from control swine. The caffeine and ATP concentration-dependency of Ca-release was determined using suction filtration with radioisotopic 45Ca as a tracer. Rates of release were determined using a rapid filtration system. Caffeine and ATP-induced Ca-release from MH-susceptible (MHS) HSR occurred at one-tenth the concentration of agonist that was required for control muscle HSR. No differences in rates and amounts of release were observed when agonist concentrations were used that caused maximum release for controls. However, at the threshold concentration of caffeine causing release for control HSR, the MHS HSR released 4-times as much Ca and at 3-times the rate of controls. These findings indicate that increased rates and amounts of Ca-release are due to the hypersensitivity of the Ca-release channel of HSR and that this abnormality can be detected using 1 gram of muscle.
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PMID:Microassay for malignant hyperthermia susceptibility: hypersensitive ligand-gating of the Ca channel in muscle sarcoplasmic reticulum causes increased amounts and rates of Ca-release. 215 20

Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine.
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PMID:The importance of calcium ions for in vitro malignant hyperthermia testing. 220 45

Excised muscles from patients with myotonia or periodic paralysis were subjected to the in vitro contracture test for susceptibility to malignant hyperthermia (MH). In a group of 44 patients, this standard test gave four positive, 10 equivocal and 30 negative results. The results for 27 control muscles from normal subjects were negative. When the test was performed with less than normal concentrations of contracture-triggering substances (caffeine less than or equal to 2 mmol litre-1, less than or equal to 2% halothane), 70% of the muscles from the patients and only 15% of the controls responded with small contractures (less than 0.2 g). These results should not be taken to indicate that the patients have the genetic trait for MH. The positive and equivocal test results, in addition to the slight contractures, may be accounted for by the electrical after-activity in the cases of pure myotonia, and by increased resting myoplasmic [Ca2+] in myotonic dystrophy. This shows that the in vitro contracture test lacks specificity.
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PMID:Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? 224 48

The adult respiratory distress syndrome developing within 24 hours in a patient who underwent suction lipectomy for body contouring under general anaesthesia is reported. During surgery, in which a total of 1.3 l of suction matter was removed, the patient became haemodynamically unstable and mildly hyperthermic. Subsequently, clinical signs and symptoms of the fat embolism syndrome developed. Aggressive haemodynamic and respiratory support over an 8-day period resulted in patient survival. Malignant hyperthermia was excluded as cause for the clinical presentation on muscle biopsy and in vitro caffeine contracture studies. Although usually complication-free, suction lipectomy may be associated with life-threatening incidents. Even suction volumes as low as 1.3 l have potential hazards, therefore the procedure merits regular postoperative observation and re-assessment.
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PMID:Fulminant adult respiratory distress syndrome after suction lipectomy. A case report. 225 20

Anaesthetic-induced increases in cytoplasmic free Ca2+ have been reported to be greater in lymphocytes from malignant hyperthermia (MH) susceptible patients than in those from controls, suggesting that this may be the basis for a less invasive test for MH susceptibility. In the present study the cytoplasmic Ca2+ concentrations of lymphocytes were monitored with indo-1 in 14 control subjects (nine fasted and five nonfasted) and five fasted MH susceptible and three fasted nonsusceptible patients, diagnosed by the halothane and caffeine contracture tests. No relationship was observed between MH susceptibility and Ca2+ concentrations in lymphocytes in the absence or presence of halothane. There was, however, a relationship in control subjects between fasting and the response of lymphocytes to halothane, with the halothane-induced Ca2+ increase being considerably larger in nonfasted subjects.
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PMID:Importance of fasting in the lymphocyte calcium test for malignant hyperthermia. 227 24


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