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 acute episode of a malignant hyperthermia-like syndrome is described which occurred after suxamethonium and halothane anesthesia in a 32 year old healthy male patient undergoing a tendon repair operation to his right thumb. Dantrolene therapy rapidly reversed the life threatening signs.
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PMID:Malignant hyperthermia--a case report. 783 72

The anaesthetic management for Caesarean delivery of a parturient with a strong family history of malignant hyperthermia (MH) is presented. Before surgery an anaesthetic machine that was in regular use was prepared by replacing all rubber or disposable components and flushing with O2 at 10 L.min-1 for one hour. Dantrolene prophylaxis was not used, and the patient received a bupivacaine and fentanyl spinal anaesthetic. Hypotension was treated with ephedrine. Current management of the MH patient no longer mandates a dedicated vapour-free machine, dantrolene is not indicated as pre-treatment, and amide local anaesthetics are considered safe. The role of vasopressors and ergot preparations is less clear.
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PMID:Anaesthesia for caesarean delivery of a malignant hyperthermia susceptible parturient. 786 20

This study examines the chronologic relationship of the biochemical and clinical development of malignant hyperthermia (MH) in susceptible swine. Four pigs previously established by challenge to be susceptible to MH were studied. Monitors included end-tidal CO2 (ETCO2), transcutaneous oxygen saturation (Spo2), intraarterial blood pressure, rectal temperature, electrocardiogram (ECG), and train-of-four twitch measurements. Calcium-selective microelectrodes were used to monitor changes in the concentration of free myoplasmic calcium ([Ca2+]i). The animals were studied in the resting state, during the development of the syndrome, and after treatment with dantrolene sodium. The increase in [Ca2+]i preceded the increase in ETCO2 that preceded a decrease in Spo2 that preceded the classic first sign, tachycardia, and all preceded the increase in rectal temperature. Dantrolene reversed all of these physiologic changes in the same order of precedence as the increase.
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PMID:Myoplasmic calcium changes precede metabolic and clinical signs of porcine malignant hyperthermia. 797 79

Intracellular free calcium is believed to play a major role in the ischaemic cascade which leads to cell death. Calcium channel blockers, which in part inhibit the influx of extracellular calcium, have been shown to be neuroprotective in both complete and focal cerebral ischaemia models. Dantrolene, an agent used in the treatment of malignant hyperthermia, is known to inhibit the release of stored intracellular calcium. Assuming that reduced levels of intracellular free calcium would improve neurologic outcome, we studied the neuroprotective potential of dantrolene. A complete cerebral ischaemia model was used to examine ten anesthetized dogs. Five were given intravenous dantrolene and five were given equal volumes of saline prior to the ischaemic event. Simultaneous occlusion of the venae cavae and ascending aorta provided eleven minutes of complete cerebral ischaemia as monitored by electroencephalography. Arterial blood gases and serum glucose levels were drawn prior to ischaemia, 5 and 20 minutes post-ischaemia, and following extubation. Forty-eight hours following the ischaemic event, neurologic outcomes were scored. No significant differences were observed between the two groups. All ten dogs had equally significant increases in serum glucose levels at 5 and 20 minutes post-ischaemia. The average neurologic outcome of the five dantrolene-treated dogs equalled the average of the five controls. These results suggest that dantrolene, alone, is not neuroprotective during complete cerebral ischaemia.
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PMID:No dantrolene protection in a dog model of complete cerebral ischaemia. 809 51

A 14-month-old boy underwent bilateral antrotomies and adenotomy for bilateral mastoiditis. During the operation, typical symptoms of malignant hyperthermia (MH) became apparent. At the time of operation, pulse oximetry and capnometry were not possible which led to a delay in making the diagnosis. Nevertheless, Dantrolene, which was available in the operating theatre, was immediately administered. The postoperative recovery was complicated by altered cerebral function (inability to concentrate), muscle exhaustion and a coagulopathy which lasted for eleven days. A muscle biopsy of the child's father was positive for MH.
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PMID:[A case report of malignant hyperthermia in a 14-month-old boy]. 814 60

The effect was examined of dantrolene, a drug for malignant hyperthermia acting through preventing release of Ca from the ryanodine-type intracellular stores in muscle cells, on ischemic delayed neuronal death in field CA1 of gerbil hippocampus. Dantrolene (1.6 mM in concentration, 3 microliters each in volume), when administered bilaterally in the lateral ventricles 30 min after reperfusion after transient forebrain ischemia for 3 min at 37 degrees C, significantly protected against the neuronal death. It is proposed that the dantrolene-sensitive (most likely, the ryanodine-type) intracellular Ca stores in CA1 pyramidal cells play a pivotal role in the development of ischemic neuronal damage.
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PMID:Dantrolene protects against ischemic, delayed neuronal death in gerbil brain. 823 63

Severe bloodstream-borne infection--i.e., sepsis--and the resulting multiorgan failure are now the most common cause of death in many intensive care units. One of the most fundamentally important and controversial issues concerning the pathophysiology of sepsis is the role of intracellular free calcium concentration ([Ca2+]i) in this disorder. Because of the critical role of calcium as an intracellular second messenger and as a potential cellular toxin, resolution of this issue is crucial. Using 19F NMR spectroscopy and the calcium indicator 5,5'-difluoro-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate we demonstrate in the intact perfused organ, the rat thoracic aorta, that [Ca2+]i in aortic smooth muscle is increased > 2-fold during sepsis. Furthermore, we determined that sodium dantrolene, a drug that decreases release of calcium from the sarcoplasmic reticulum and that is lifesaving in malignant hyperthermia (a disorder due to increased [Ca2+]i), is able to reduce the elevated [Ca2+]i in sepsis to control values when added in vitro or when given in vivo to the animal. These results suggest that an increase in [Ca2+]i is an early event in sepsis and that increased [Ca2+]i may be responsible for, or contribute to, cellular injury. Dantrolene may offer a therapeutic strategy in the treatment of sepsis.
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PMID:Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis? 848 13

Hyperthermia and profuse perspiration are rarely absent in severe cases of scorpion envenomation. Based on these observations, the aim of this study was to determine the therapeutic effects of dantrolene, on experimental poisoning by the venom of Androctonus australis hector. Dantrolene is a directly acting muscle relaxant which lowers the body temperature in malignant hyperthermia. The results indicate that the early use of this drug raises the LD50 in experimentally poisoned mice. If these results are transposable to humans, dantrolene could be a useful therapeutic adjuvant.
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PMID:Use of dantrolene in experimental scorpion envenomation by Androctonus australis hector. 853 4

Dantrolene effectively treats malignant hyperthermia (MH) hut the current form, Dantrium, must be dissolved to a 0.33 mg/mL, pH 9.5 solution. This study describes lecithin-coated microcrystal formulations of sodium dantrolene (MC-NaD) and neutral dantrolene (MC-D) which reconstitute to 200 mg/mL within 1 min. In rats, the pharmacokinetics and pharmacodynamics of MC-NaD and Dantrium were similar: half-lives of 3.1 h, volume distributions of 0.54 and 0.59 L/kg, and 95% effective dose (ED95) values for depression of skeletal muscle twitch height (ED95T) of 2.6 +/- 0.7 and 2.8 +/- 0.5 mg/kg. In swine, the ED95T values for MC-NaD and Dantrium were also similar (2.8 +/- 0.4 vs 2.7 +/- 0.6 mg/kg), but MC-D and Dantrium were only similar at doses more than 2.5 mg/kg (ED95T: 3.5 +/- 0.4 vs 2.7 +/- 0.5 mg/kg). In susceptible swine, MC-NaD successfully treated five of six MH episodes and prevented MH in three of four swine. However, MC-NaD caused marked pulmonary hypertension in swine, while MC-D caused only a mild response that was eliminated by filtration. Likewise, MC-D caused no pulmonary response in dogs. These observations suggest that MC-D has potential to improve the treatment of MH.
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PMID:Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: an investigation in rats, dogs, and swine. 861

Malignant hyperthermia (MH) is a naturally occurring disease of stress-susceptible (SS) pigs subjected to triggering agents or stress. MH is characterized by accelerated muscle metabolism and hyperthermia due to abnormally increased myoplasmic Ca2+ levels. Dantrolene is used for the treatment of MH and acts by reducing the myoplasmic Ca2+ levels. Muscle lesions can be induced by experimental restraint stress in SS pigs and are suspected to be caused by increased myoplasmic Ca2+ levels. This experiment was performed in order to study if stress induced muscle lesions could be reduced by dantrolene. Nine SS pigs were exposed to experimental restraint stress provoked by a 12 min intravenous (i.v.) infusion of the depolarizing myorelaxant succinylcholine. Five pigs were orally dosed with dantrolene (5 mg/kg), twice, about 24 and 5 h before the stress (group A). The other four pigs were treated with a single i.v. infusion of dantrolene (5 mg/kg), 30 min before stress (group B). The animals were necropsied approximately 48 h after the stress and 24 skeletal muscles were examined macro- and microscopically. No clinical signs of MH occurred during the experiment. The required dose of succinylcholine was higher in group B (0.08 mg/kg/min) than in group A (0.03 mg/kg/min) indicating decreased sensitivity to succinylcholine in SS pigs after i.v. treatment with dantrolene. The pigs in group A, but not in group B showed slightly increased serum levels of creatine kinase (CK) and aspartate aminotransferase (ASAT) at time of necropsy. A significant reduction in acute muscle lesions was observed in both groups, especially in group B, when compared with SS pigs subjected to restraint stress, but not treated with dantrolene. The muscle lesions induced by the stress model are considered to be induced by increased myoplasmic Ca2+ levels since they can be reduced by dantrolene treatment.
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PMID:The reduction of skeletal muscle lesions after experimental stress in stress-susceptible pigs protected with dantrolene. 882 90


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