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)

Piglets less than 8 wk of age that are known by genotype to be malignant hyperthermia-susceptible (MHS) do not usually develop characteristic hyperthermia and limb muscle rigidity in response to a brief halothane exposure (5 min of 3%). To determine whether a malignant hyperthermia (MH) episode could nevertheless be provoked by a more rigorous challenge, both genetically MHS (Pietrain) and normal (Yorkshire) 5-wk-old piglets were exposed to a combined halothane-succinylcholine challenge. Only two of eight MHS piglets developed limb rigidity; however, all MHS piglets (and no normal piglets) developed clinical signs of MH episode initiation during the 30-min challenge. Temperatures rose from 37.4 to 38.6 degrees C in MHS piglets while falling slightly in normal piglets. In MHS piglets, venous pH fell from 7.46 +/- 0.02 to 6.88 +/- 0.07, PVCO2 rose from 36 +/- 2 to 126 +/- 17 mmHg, and plasma concentration of K+ rose from 4.0 +/- 0.1 to 7.1 +/- 0.6 mM, whereas all values remained stable in normal piglets. Muscles removed from the same piglets before the halothane-succinylcholine challenge were exposed to halothane in vitro. The muscles from genetically MHS piglets responded to halothane with characteristic depression of tetanic tension and prolonged tetanus relaxation time but did not develop halothane-induced contractures. We conclude that, in the absence of either halothane-induced limb rigidity or in vitro contractures, these young animals were still susceptible to potentially fatal MH episodes on exposure to appropriate triggering agents. The MH defect is apparently partially masked in piglets and expressed fully only in older pigs.
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PMID:Halothane sensitivity of young pigs in vivo and in vitro. 237 22

Malignant hyperthermia is a threat to the life of the surgical patient. It is a pharmacogenic disease that is brought on by contact with certain drugs and is manifest by a hypermetabolic crisis with tachycardia, ventricular ectopy, metabolic acidosis, and a rapid rise in body temperature. Muscle rigidity may or may not be present. Thanks to a reliable porcine animal model of malignant hyperthermia, dantrolene sodium has been found to be effective in the prevention and treatment of malignant hyperthermia. In this article a case report of malignant hyperthermia occurring in an office surgery suite is presented. The patient was 37 years old and underwent a routine septorhinoplasty under general anesthesia. The operation was complicated by ventricular ectopy, rapid rise in body temperature, and muscle rigidity at the end of the case. The malignant hyperthermia aborted spontaneously after 30 minutes; dantrolene was not given.
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PMID:Malignant hyperthermia in an office surgery suite: a case report. 274 52

To provide information regarding the cause of the muscle rigidity in malignant hyperthermia-susceptible (MHS) pigs, the Ca-induced Ca-release mechanism of the sarcoplasmic reticulum (SR), the Ca uptake by the SR, and the Ca-activated tension production of the contractile system were examined in skinned skeletal muscle fibers from MHS and normal pigs. In muscles of MHS pigs, the rate of Ca-induced Ca release was significantly higher than in normal muscle. The potentiation effect on Ca-induced Ca release by halothane and caffeine did not differ appreciably between MHS and normal fibers. The rate of Ca uptake by the SR and the Ca sensitivity of the contractile system of MHS fibers were not different from those of normal fibers, and halothane in an anesthetic concentration exerted no effect on them. Dantrolene inhibited the Ca-induced Ca release at 38 degrees C. These results suggest that the principal cause of malignant hyperthermia (MH) in MHS pigs is due to the enhancement of the Ca-induced Ca-release mechanism of the SR of the skeletal muscle.
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PMID:Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle. 291 63

Thyroid crisis on induction of anaesthesia was treated with dantrolene, because of a mistaken diagnosis of malignant hyperthermia. There was immediate improvement after dantrolene with reduction in muscle rigidity, mental confusion and pyrexia. High circulating T4 has an effect on calcium flux across the sarcoplasmic reticulum and dantrolene may inhibit this pathological mechanism. We suggest the same dosage regimen as is used in the treatment of malignant hyperthermia.
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PMID:Acute thyroid crisis on induction of anaesthesia. 292 4

Heat stroke victims lack thermoregulatory control. Treatment includes immediate cooling, circulatory support and monitoring for secondary complications. Neuroleptic malignant syndrome is a complication of neuroleptic drug therapy; skeletal muscle hypertonicity helps distinguish this entity from heat stroke. Malignant hyperthermia should be considered in any patient who is under physiologic or anesthetic stress and develops hyperthermia plus skeletal muscle rigidity, tachypnea, hypoxia, tachycardia and hyperkalemia.
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PMID:Hyperthermic syndromes. 328 39

We report a family in which two sisters with myotonia congenita (MyC) were referred for malignant hyperthermia (MH) evaluation after each developed muscle rigidity with anesthesia. Halothane contracture testing of skeletal muscle in both was consistent with MH susceptibility. A third sister without clinical evidence of MyC was negative on contracture testing. These results suggest an association between MyC and MH susceptibility.
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PMID:Malignant hyperthermia in myotonia congenita. 336 83

The use of dantrolene to reverse severe unexplained postanaesthetic muscle rigidity in a previously "healthy" 13-year-old male is described. Anaesthesia was induced with thiopentone. After intubation with pancuronium, the patient had an entirely uneventful nitrous oxide, oxygen and halothane anaesthetic. Immediately following reversal of the relaxant, the patient developed generalized muscle tightness and rigidity involving the trunk and extremities. This was prolonged and severe enough to interfere with adequate ventilation. The patient also had a prolonged recovery from the anaesthetic. After ruling out malignant hyperthermia and some other causes of rigidity, a tentative diagnosis of myotonia was made. The symptoms responded to IV dantrolene in a total dose of 2.0 mg.kg-1. Further testing failed to establish a definite diagnosis. Dantrolene could be a useful drug in treating such unexplained muscle rigidity.
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PMID:Reversal of prolonged postoperative muscle rigidity by dantrolene: a case report. 340 20

An account is given of unusual course of a hyperthermic crisis in a 23-year-old male who underwent repeated anesthetics. As yet little has been reported about Isoflurane, which we presume to have been the triggering agent. In this case only the surgically untreated lower extremity developed rigor, with which malignant hyperthermia is associated, whereas the surgically treated extremity, where circulation had been stopped with a tourniquet, remained unaffected. Rigor and contracture of the affected extremity were so severe that they led to a compartment syndrome, necessitating fasciotomy. No observation of this kind has been published before. In addition to a discussion of this dissociated effect in malignant hyperthermia, a detailed account of the course of the crisis is given.
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PMID:[Malignant hyperthermia. An unusual course of a rare disease]. 340 97

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Purebred Pietrain pigs presumed (on the basis of pedigree) to be homozygous for malignant hyperthermia (MH) susceptibility were subjected to a 3% halothane challenge test. A few (6%) pigs that should have been MH susceptible on the basis of parental genotype did not develop muscle rigidity in response to repeated halothane tests. Three of these animals were brought into the laboratory, and muscle biopsy specimens were obtained for in vitro analysis. Bundles of intact muscle cells dissected from biopsy specimens were electrically stimulated, and mechanical responses were monitored during exposure to halothane. In all instances, the muscle bundles from the halothane-negative (ie, not sensitive to halothane), but genetically susceptible, pigs gave in vitro responses that were similar of those of halothane-positive MH-susceptible pigs in that tetanic tension was depressed, tetanus relaxation was slowed, and small contractures were produced upon halothane exposure. Thus, the presence of a halothane-sensitive abnormality in the skeletal muscles, in and of itself, is not always sufficient for development of in vivo muscle rigidity during a brief halothane test. Furthermore, when the halothane testing of pigs is conducted by recommended techniques, false negatives still occur in a small percentage of the genetically MH-susceptible animals.
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PMID:Porcine malignant hyperthermia: false negatives in the halothane test. 356 5


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