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)

An 18-month-old boy with congenital muscular dystrophy began to develop clear signs of the malignant hyperthermia syndrome after 85 min of halothane/nitrous oxide anaesthesia. Dantrolene, 2 mg/kg i.v., was immediately effective, but temperature, heart rate and carbon dioxide production were all increased for 2 days postoperatively in spite of repeated dantrolene administration.
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PMID:Malignant hyperthermia in a myopathic child. Prolonged postoperative course requiring dantrolene. 714 63

Dantrolene, a skeletal muscle relaxant, has been proven prophylactic and therapeutic for malignant hyperthermia (MH) in swine. This study examined the feasibility of using a dantrolene dose response as measured by indirectly evoked foretoe twitch depression as a means to safely discriminate MH susceptibility in swine. The effect of halothane on the dantrolene response was quantified. Subjects were five Poland China malignant hyperthermia susceptible (MHS) and five Hampshire malignant hyperthermia resistant (MHR) swine. Dantrolene dose response was determined twice in each anaesthetized subject, once with thiopentone and subsequently with thiopentone and halothane. Dantrolene in incremental doses, 0.15 mg.kg-1, was given to a cumulative dose of 2--3 mg.kg-1. Under thiopentone anaesthesia, the dantrolene dose responses were similar in MHS and MHR animals. The presence of halothane augmented dantrolene twitch depression in MHS but not MHR animals when compared to their response under thiopentone. Under halothane, the MHS animals had significantly augmented dantrolene response compared to MHR pigs, but three MHS animals had developed the MH syndrome prior to receiving dantrolene. We conclude that dantrolene muscle relaxant dose response cannot be used as a diagnostic test for MHS in swine. Halothane augments dantrolene twitch depression in MHS swine.
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PMID:Porcine malignant hyperthermia--failure of dantrolene dose response to diagnose susceptibility (halothane effect). 735 86

In connection with malignant hyperthermia the afflicted girl and her blood relations from 4 generations were investigated. Noteworthy in the case histories were fractures following minor traumas of the brother and epilepsy in 3 cases. The serum CK was increased in 6 individuals. The EMG showed alterations in 3 participants which pointed to discrete myopathy. The muscle biopsies of patient and parents were normal under microscope and electron microscope. The findings are consistent to the accepted theories of hereditary mode. Due to inadequate means of predicting the onset, early recognition and treatment of malignant hyperthermia remain essential. Promising prohibitive and curative results have been brought about with Dantrolene in animal experiments.
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PMID:[Malignant hyperthermia. II. Investigation of the patient's family (author's transl)]. 737 29

Ryanodine toxicity in animals has been suggested to constitute a model of malignant hyperthermia. Dantrolene is known to block the development of malignant hyperthermia triggered by halothane in susceptible swine. The authors studied the influences of dantrolene and halothane on the effects of ryanodine in vitro in isolated rat diaphragm muscle segments, and in vivo in mice, to explore the validity of this model. In the diaphragm experiments, dantrolene was found to block or delay the development of contractures produced by ryanodine and to delay the potentiation of ryanodine-induced contractures caused by halothane. In mice, ryanodine at various dosages was injected and animals surviving after one hour were examined. Such survivors appeared grossly to be normal, and may constitute a model for the malignant hyperthermia patient. They were found to be susceptible to halothane and to succinylcholine, being killed by treatment with these two agents at dosages that were not lethal to control mice. Pretreatment of mice for 48 hours with orally administered dantrolene, followed by injection of ryanodine and then halothane anesthesia, decreased the lethality of ryanodine but did not reduce the number of deaths caused by the subsequent exposure to halothane. That the effects of ryanodine in vitro and in vivo are diminished and potentiated by dantrolene and halothane, respectively, would suggest that the ryanodine toxicity model of malignant hyperthermia may have validity and is worthy of further study. A prediction from this model is that the terminal cisternae of skeletal muscle sarcoplasmic reticulum may be altered in MH.
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PMID:Modification of ryanodine toxicity by dantrolene and halothane in a model of malignant hyperthermia. 742 33

Early clinical recognition, confirmed by blood gases analysis has permitted successfull management of a case of severe malignant hyperthermia. The authors stress the crucial importance for the theatres area to be fitted up with a huge crushed ice making device and with a large supply of cold saline solution. Due to the lack of easy and reliable preoperative screening test it is mandatory to put high risk patients on Dantrolene therapy when elective surgery is planned.
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PMID:Uneventful recovery in a case of severe malignant hyperthermia. 746 39

Skeletal muscle may release creatine kinase (CK) during a malignant hyperthermia (MH) episode; however, muscle damaged during surgery may also release CK. This study examined the overlap between peak plasma CK levels in patients suspected of having had a MH episode (data obtained from North American MH Registry) and previously published CK changes occurring after common surgeries. For patients who were subsequently proven to be MH positive by muscle biopsy, there was considerable overlap. This was most significant with surgeries having substantial tissue damage, such as major vascular surgery and abdominal surgery. Overlap was much less with minimally invasive surgery, such as cystoscopy. Approximately 30% of MH positive patients treated with dantrolene had peak CK in the range of most surgical procedures, and approximately 50% of MH positive patients not given succinylcholine had peak CK similar to those of most surgical procedures. Dantrolene did not significantly alter peak CK in MH positive patients; however, succinylcholine was associated with significantly higher peak CK. These data suggest that patients who have had an acute MH episode during a surgical procedure may have peak CK values within the range of CK values expected from the procedure itself.
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PMID:Creatine kinase alterations after acute malignant hyperthermia episodes and common surgical procedures. 748 44

Malignant hyperthermia (MH) may result from increased intracellular calcium concentrations. Increased 1,4,5-IP3 concentrations could mediate this increase in Ca2+. In this study we measured inositol polyphosphates in selectively bred MH susceptible (MHS) and MH non-susceptible (MHN) swine. MH crisis was induced by halothane challenge, and dantrolene was administered in order to measure inositol polyphosphates after MH reversal. Muscle biopsies of skeletal muscles of the hind limbs were obtained in random order and inositol polyphosphates determined by high pressure liquid chromatography using a metal dye detection method. Inositol polyphosphates were determined in three groups: (1) MHS vs MHN basal, (2) during MH crisis induced by halothane and (3) following treatment with dantrolene after halothane challenge. Clinical variables (P(_)VO2, P(-)VCO2, PE'CO2 and pH) indicated that MH was readily induced in MHS swine. Basal concentrations of all inositol polyphosphates were higher in MHS swine compared with MHN swine. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 concentrations increased in MHS animals compared with the respective baseline values, whereas no changes in MHN animals could be detected. Dantrolene administration decreased inositol polyphosphate concentrations in MHS swine. MHN swine showed no changes in inositol polyphosphates after dantrolene. These findings indicate that inositol polyphosphates may be involved in metabolic changes after triggering and treatment of MH.
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PMID:Alterations of inositol polyphosphates in skeletal muscle during porcine malignant hyperthermia. 748 90

Dantrolene, an intracellularly acting skeletal muscle relaxant, inhibits Ca2+ release from the sarcoplasmic reticulum during excitation-contraction coupling by an unknown mechanism. The drug is used to treat malignant hyperthermia, a genetic sensitivity to volatile anesthetics which results in the massive release of intracellular Ca2+ from affected skeletal muscle. We hypothesize that determination of the site of action of dantrolene will lead to further understanding of the regulation of sarcoplasmic reticulum calcium release. We report the identification of specific dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum using a rapid filtration binding assay for [3H]dantrolene. The binding isotherm in the heavy sarcoplasmic reticulum fraction indicates a single binding site with a Kd of 277 +/- 25 nM and a Bmax of 13.1 +/- 1.5 pmol/mg of protein. Pharmacological specificity is characterized by inhibition of [3H]dantrolene binding with unlabeled dantrolene, or azumolene, a physiologically active congener, but not with aminodantrolene, which is physiologically inactive. Drug binding is maximal at pH 6.5-7.5, requires no Ca2+ or Mg2+, and is inhibited by salt concentrations above 100 mM. [3H]Dantrolene binding is greatest in the sarcoplasmic reticulum, which contains the ryanodine receptor, the primary calcium release channel. No binding is detected in the fractions enriched for sarcolemma or transverse tubules. We suggest that dantrolene inhibits calcium release from the sarcoplasmic reticulum by either direct or indirect interaction with the ryanodine receptor.
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PMID:Identification of dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum. 762 73

Malignant hyperthermia is a potentially fatal condition inducible by volatile anaesthetics and/or suxamethonium in genetically susceptible individuals. A disturbed calcium homeostasis in skeletal muscle (possibly in the ryanodin receptor) results in elevated myoplasmatic calcium. The latter causes muscle contraction and a hypermetabolic state, clinically observed as rigidity, fever, hypercarbia, metabolic acidosis and hyperkalemia. Arythmia ensues. Dantrolene inhibits the release of calcium and can halt the process if the diagnosis is made early. A fatal incident of probable malignant hyperthermia in a 13 year old boy is described and evaluated according to a multifactorial clinical grading scale. The value of the in vitro contracture test to diagnose malignant hyperthermia is discussed. Suggestions concerning the treatment of masseterspasm rigidity, an acute episode of malignant hyperthermia, and safe anaesthesia for susceptible patients are presented.
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PMID:[Malignant hyperthermia--still a current and dangerous problem]. 777 Aug 53

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 mumol.l-1 ryanodine. After pretreatment with 1 mumol.l-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8 +/- 1.8 min) and MHN (46.0 +/- 4.2 min) muscle specimens than after ryanodine alone (MHS 4.8 +/- 0.7 min. (MHN 13.7 +/- 0.9 min). They were no longer observed in either group after pretreatment with 5 mumol.l-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependently, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.
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PMID:Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene. 779 13


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