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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 a life threatening complication following anaesthesia with potent inhalational agents and suxamethonium. The signs of MH are caused by increased metabolism and secondary stimulation of the sympathetic nervous system due to uncontrolled, high intracellular concentrations of calcium in skeletal muscle. The hyperthermia is secondary to the increased energy turnover. Calcium release from the sarcoplasmic reticulum is increased due to a low threshold for release and prolonged opening of the calcium channel upon normal stimulation. The gene encoding the calcium channel is localized on chromosome 19 in humans, and a substitution of cysteine for arginine has recently been described in one family with MH.
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PMID:[Malignant hyperthermia]. 131 Mar 56

Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled calcium flux in the skeletal muscles resulting in a variable clinical syndrome of muscle rigidity, respiratory and metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the ryanodine receptor, a large protein which comprises the calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known myopathies and other muscle related problems, such as acute rhabdomyolysis or idiopathic persistently elevated creatine kinase, suggest a possible association of MH with a variety of neuromuscular diseases and stress syndromes. This association is very strong in the case of central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (King-Denborough syndrome, Duchenne muscular dystrophy) or unlikely to be associated (myotonia congenita, sudden infant death syndrome, limb girdle dystrophy, neuroleptic malignant syndrome, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hyperthermia and neuromuscular disease. 148 40

In malignant hyperthermia, dantrolene, a drug assumed to possess calcium channel blocking properties, effectively suppresses supraventricular and ventricular arrhythmias. To investigate antiarrhythmic properties of dantrolene, six patients (three women and three men, age 42 +/- 18 yr) with symptomatic atrioventricular (AV)-nodal reentry tachycardia were studied. Electrocardiographic measurements included sinus cycle length, PQ-interval, width of the QRS-complex, and QT- and rate-corrected QT-interval. During the electrophysiologic study, effective refractory periods of the right atrium, AV node, right ventricle, and AV-nodal conduction intervals were determined, and AV-nodal reentry tachycardia was induced in all patients. Dantrolene was administered intravenously over a period of 15 min at doses of 1.0, 1.5, or 3.0 mg/kg in two patients each. The dosage was not further increased because of side effects at the dose of 3.0 mg/kg. After the infusion of dantrolene, the electrocardiographic measurements and electrophysiologic study were repeated. The plasma concentrations of dantrolene ranged from 1.69 to 6.61 micrograms/ml at the time of the electrophysiologic study. After dantrolene administration, the sinus cycle length shortened from 686 +/- 80 to 622 +/- 55 ms (P less than 0.05). No significant changes of any other parameter could be demonstrated after intravenous dantrolene. AV-nodal reentry tachycardia remained inducible in all patients without change of the tachycardia cycle length and without change in coupling intervals of tachycardia-inducing extrastimuli. Antiarrhythmic properties of dantrolene could not be demonstrated in patients with AV-nodal reentry tachycardia at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous dantrolene does not exhibit calcium channel blocking effects on the cardiac conduction system in humans. 192 68

The effects of diltiazem (1 microM) and nifedipine (1 microM) were examined separately on the in vitro halothane tests for malignant hyperthermia (MH) susceptibility. Eighteen patients with MH susceptibility were diagnosed as MH-susceptible (MHS) according to the protocol of the European MH Group. In addition, halothane tests were carried out in the presence of either diltiazem (ten patients) or nifedipine (eight patients). These two calcium channel blockers significantly reduced the halothane contracture. Furthermore, in five of the ten MHS patients tested in the presence of diltiazem as well as in five of the eight MHS patients tested in the presence of nifedipine the halothane contracture test could be classified as negative. It is concluded that the presence of clinical concentrations of either diltiazem or nifedipine in the muscle bath affects the in vitro discrimination for MH susceptibility to halothane.
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PMID:Diltiazem and nifedipine reduce the in vitro contracture response to halothane in malignant hyperthermia-susceptible muscle. 237 58

Preparing skeletal sarcoplasmic reticulum from both normal and malignant hyperthermia susceptible pigs, the effects of various drugs on the passive calcium permeability of these sarcoplasmic reticulum preparations were studied. It was found that, in the absence of halothane, the permeability of heavy sarcoplasmic reticulum prepared from malignant hyperthermia susceptible pigs was much higher than that of normal pigs. It was observed that halothane, at concentrations above 10 microM (well below anesthetic concentrations, which are on the order of 1 mM), increased the permeability of sarcoplasmic reticulum. The Hill coefficient of the effect of halothane ranged from 1.96 to 2.25, suggesting that some kind of cooperativity was involved in this reaction. The effects of caffeine were similar to those of halothane. Inhibitors, such as tetracaine and ruthenium red inhibited both the calcium permeability and the halothane-induced increment. The Hill coefficient of the effect of tetracaine was 1.75. The mode of inhibition suggests that tetracaine directly binds with the calcium channel to inhibit the calcium efflux. On the contrary, dantrolene did not affect the calcium permeability of the sarcoplasmic reticulum. However, it inhibited the halothane-induced and caffeine-induced increments of the permeability. The Hill coefficient of inhibition by dantrolene ranged from 2.3 to 3.9, suggesting that several molecules of dantrolene may interact cooperatively with one calcium release channel to inhibit the effect of halothane. These results suggest that dantrolene has a unique inhibitory action, which may be related to its efficacy in ameliorating the syndrome of malignant hyperthermia.
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PMID:Effects of halothane, caffeine, dantrolene and tetracaine on the calcium permeability of skeletal sarcoplasmic reticulum of malignant hyperthermic pigs. 243 28

We have studied the ability of the calcium channel antagonist diltiazem to inhibit and reverse the porcine malignant hyperpyrexia (MH) syndrome. Pretreatment with diltiazem modified an MH response. Treatment with diltiazem was partially effective against a mild (or early) MH response. Diltiazem should not be considered to be an effective therapeutic agent for MH and should not displace the use of dantrolene.
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PMID:Effect of diltiazem on porcine malignant hyperpyrexia induced by suxamethonium and halothane. 273 Aug 29

Clinical uses of calcium channel blockers are expanding. In addition to the established uses in patients with arrhythmias, angina pectoris or hypertension, newer and to some extent investigational uses indicate widespread application. For instance, their use has been reported in hypertrophic cardiomyopathy and cold cardioplegia, as well as in pulmonary hypertension, antiplatelet therapy, asthma, achalasia and oesophageal spasm, increased intraocular pressure and in cerebral vasospasm. Their use in obstetrical practice has been proposed. Thus, the presentation of a patient who is treated with calcium channel blockers and who requires anaesthesia will become more common. Calcium channel blockers may, under certain circumstances, potentiate haemodynamic and MAC depressive effects of inhalation agents. There is also evidence that the effects of neuromuscular blocking agents may be potentiated. The anaesthetist should be aware that the potential for interactions exists with digoxin, propranolol, quinidine, theophylline or dantrolene. Of interest and some significance are the anaesthetic implications of pathophysiological alterations that can be induced by calcium channel blockers, by affecting lower oesophageal tone, intracranial hypertension, bronchomotor tone (asthma), muscular dystrophy, neuromuscular function, hypoxic pulmonary vasoconstriction, malignant hyperthermia, inhibition of platelet aggregation and hyperkalemia. Despite these significant potential anaesthetic implications and because, at this time, in some instances withdrawal has clearly demonstrated increase in the signs of myocardial ischaemia, it would not seem necessary to recommend preoperative discontinuation of calcium channel blocker medication in patients presenting for anaesthesia. It is, however, appropriate that there is a high index of awareness of potential problems, unless there is some modification in inhalation anaesthetic concentrations and neuromuscular blocker dosage. Monitoring of cardiovascular and neuromuscular functions is essential. Calcium channel blockers would appear to be currently the drugs of choice for angina pectoris, arrhythmias or hypertension in patients with associated chronic obstructive pulmonary disease.
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PMID:Anaesthetic implications of calcium channel blockers. 286 80

New publications on malignant hyperthermia (MH), with direct clinical importance, are reported. Since even in the recent past patients have died from MH in spite of therapy with dantrolene, the effectiveness of dantrolene is discussed in particular. Atypical clinical pictures of MH are presented. Special psychiatric syndromes (malignant neuroleptic syndrome and acute febrile catatonia), rhabdomyolysis with myoglobinuria following strenuous exercise or exposure to heat are mentioned, as these disorders appear to be related to MH, in that they are hypermetabolic syndromes implying a muscle membrane dysfunction. The role of slow calcium channel blockers and 5-hydroxytryptamine antagonists as prophylactic or therapeutic agents in MH is discussed. A schedule describing how to diagnose, treat and prevent MH, considering recent advances, is presented.
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PMID:[New findings and experiences in the field of malignant hyperthermia]. 293 19

We have investigated in malignant hyperthermia susceptible swine in vivo the effects on halothane initiation of the MH syndrome and on the established syndrome of five calcium channel blocking drugs--nifedipine, nisoldipine, diltiazem, verapamil and flunarazine. Nifedipine alone caused attenuation of halothane-initiated malignant hyperthermia to the extent of blocking onset of the syndrome in 29% of animals for the 60 minute period of exposure. In the face of the established malignant hyperthermia syndrome, all the drugs tested were therapeutically completely ineffective.
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PMID:The effects of calcium channel blocking drugs on halothane initiation of malignant hyperthermia in MHS swine and on the established syndrome. 339 13

Calcium pulse additions to isolated SR membranes can cause a reversible efflux of calcium. The threshold level of calcium loading at which calcium efflux occurs is lower for SR membranes isolated from malignant hyperthermia susceptible (MHS) swine. Dantrolene, a unique muscle relaxant, had no effect on threshold calcium load, amounts and rates of calcium release from SR isolated from control and MHS skeletal muscle. It is concluded that the putative calcium channel through which this calcium pulse-induced calcium release mechanism occurs is not affected by dantrolene under these experimental conditions.
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PMID:Dantrolene does not block calcium pulse-induced calcium release from a putative calcium channel in sarcoplasmic reticulum from malignant hyperthermia and normal pig muscle. 632 Dec 31


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