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 a rare syndrome seen when susceptible individuals are exposed to one or more of various triggering agents, most commonly a depolarizing muscle relaxant or an inhalational anaesthetic agent. There is a dramatic rise in metabolic rate and oxygen consumption which if not treated promptly and effectively results, in the majority of cases, in the patient's death. Fatal responses to physical stress associated with the familial muscular disease known as MH are being increasingly reported in situations not related to anaesthesia or drugs. Moreover, cases of MH were recognized to be "induced" in the postoperative period when obviously the major effects of anaesthesia were no longer of important consideration. Therefore a more expanded concept of MH seems to develop, including the assumption that one of the other factors in MH is stress. The implication of this extends far beyond the scope of anaesthesiology. The acute hypermetabolic state in MH, resulting in acidosis, heat production and muscular activity is probably due to an inability to control calcium concentration within the skeletal muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. The susceptibility to develop MH is controlled by several genetic factors. Evaluation of affected families is guided by in vitro analysis of drug-induced contractures in muscle biopsy specimens; a practical and reliable non-invasive test to predict the susceptibility is still being sought. At the present time there is incontrovertible evidence that the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis of MH. A concept for the treatment of MH and guidelines for the management of a patient at risk are presented; medico legal aspects of the complication are stressed.
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PMID:[Malignant hyperthermia]. 634 13

Anesthetic-induced malignant hyperthermia (MH) originally attracted scientific interest because of the associated high fatality rate. Recently, the introduction of treatment with the muscle relaxant dantrolene sodium has dramatically reduced the frequency of death from MH. Nonetheless, diagnosing MH susceptibility remains a problem because it necessitates a muscle biopsy specimen that must be tested in a specially equipped laboratory. Thus, diagnosis is both expensive and invasive. Development of simpler and less invasive methods would be aided by identification of the primary defect underlying initiation of MH. Our understanding of whole-body responses during MH episodes and the development of treatment with dantrolene sodium have both resulted from studies of porcine MH, which is similar to the syndrome in humans. Investigations of porcine MH have demonstrated that the defect responsible for initiation of MH must be located in skeletal muscle. Many abnormal responses of MH muscle have been identified after exposure to triggering agents. These defects contribute to the maintenance and amplification of the MH episode once it has been initiated. The primary defect responsible for triggering this complex chain of events, however, has thus far eluded definition.
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PMID:Malignant hyperthermia: responses of skeletal muscles to general anesthetics. 635 73

Two cases of malignant hyperthermia are described where the earliest sign was a rise in the end-tidal CO2 concentration. This led to nearly immediate detection and adequate treatment with sodium dantrolene. These cases demonstrate the efficacy of monitoring end-expired CO2 concentrations in patients at risk from malignant hyperthermia, as well as a means for following the adequacy of treatment.
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PMID:End-tidal CO2 monitoring. Its use in the diagnosis and management of malignant hyperthermia. 643 67

The time courses of changes in amplitudes of muscle action potentials (MAPs) obtained from gastrocnemius and soleus muscles by 5 Hz prolonged tibial nerve stimulation were studied. Subjects included muscular dystrophy (MD), spinal muscular atrophy, Issacs syndrome, idiopathic muscle spasms, psychiatric disorders such as autism and schizophrenia, and normal controls. In normal subjects, MAPs obtained at 5 minutes from gastrocnemius muscles was 87-102% of those at initiation of the stimulation. In soleus muscles, MAPs at 5 minutes was 95-105% of those at the beginning. In gastrocnemius muscles, MAPs increased in disorders such as Duchenne MD, Fukuyama type congenital MD, facioscapulohumeral MD, myotonic dystrophy, dermatomyositis, Kugelberg-Welander syndrome, viral myelitis, malignant hyperpyrexia, autism and schizophrenia. In soleus muscles, the increase of MAPs was demonstrated in Duchenne MD, Fukuyama type congenital MD, myotonic dystrophy and autism. MAPs remained within normal range in infants with Werdnig-Hoffman disease, Issacs syndrome and idiopathic muscle spasms. In two cases with Duchenne MD, MAPs obtained from gastrocnemius muscles reduced in amplitudes by the administration of dantrolen sodium. While the pathogenesis of the increased MAPs is not clear, several possible factors are discussed. It is considered that this 5 Hz examination may provide an important information for detecting the effect of dantrolen sodium on Duchenne MD, and it is also suggested that the examination will be a useful test for finding latent malignant hyperpyrexia.
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PMID:Increased muscle action potentials by 5 Hz prolonged nerve stimulation in neurological and neuromuscular disorders--clinical usefulness for detecting underlying pathophysiology. 648 78

Malignant hyperthermia (MH) can be a catastrophic and sometimes fatal reaction in certain susceptible individuals who are exposed to skeletal muscle relaxants such as succinylcholine and/or certain inhalation anesthetics such as halothane. In an attempt to develop a safe, simple in vivo test to identify the at-risk patients, repetitive nerve stimulation (RNS) and electromyographic (EMG) studies were performed on 9 patients with MH, 15 patients suspected of having MH, and 9 control subjects. Serial recordings were made following injections of caffeine sodium benzoate, succinylcholine, and halothane at the test site. Measurements were done on the amplitude of the evoked compound motor action potentials (CMAP), on RNS, and on the number of negative peaks of motor unit potentials (MUP) on maximum EMG recruitment. The results showed the effects of the drugs on amplitudes of the CMAPs to be significant (P less than 0.001) in all three groups, but no significant differences were found among the groups (P = 0.93). The negative peaks of MUP on EMG recording showed a significant difference upon introducing succinylcholine (P less than 0.001), and significant interaction effects of the treatment by the patient group. Preliminary comparisons of in vivo tests with in vitro contracture tests in nine patients showed good correlation.
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PMID:Electrodiagnostic tests in the detection of malignant hyperthermia. 654 7

Electron microprobe analysis was used to determine cellular concentrations of potassium and sodium in renal cortical cells of hypertensive rats of the Milan strain (MHS) and spontaneously hypertensive rats of the stroke prone strain (SHRSP) and their respective controls. Potassium concentrations in proximal and distal tubular cells were similar in both strains of hypertensive rats compared with their normotensive controls. In MHS rats proximal tubular cell sodium concentration was lower than in controls by 3.1 mmol/kg ww, whereas in both proximal and distal tubular cells of SHRSP sodium concentrations were higher than in controls by 5.3 and 4.3 mmol/kg ww, respectively. These results indicate that changes in the transport characteristics of the renal tubular epithelium are a feature of both models of hypertension.
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PMID:Sodium and potassium concentrations of renal cortical cells two animal models of primary arterial hypertension. 659 94

Young pre-hypertensive rats of the Milan strain (MHS) have a faster glomerular filtration rate (GFR) and a higher urine flow in vivo than matched normotensive controls (MNS). Kidneys from both MHS and MNS at different ages were perfused in vitro with cell-free artificial medium, in order to further clarify the nature of these differences, in the absence of extrarenal uncontrolled factors. Isolated kidneys from young MHS showed a faster GFR, a larger tubular Na+ reabsorption and urine flow as compared to matched MNS: such differences endured throughout the 2 h of perfusion. These results support an intrinsic kidney abnormality as causing the above described differences between young rats of the two strains. Isolated kidneys from adult MHS showed faster GFR, higher renal perfusion flow and urine flow, yet similar tubular Na+ reabsorption when compared to MNS. Moreover a faster decay in kidney function was observed in the experiments with MHS. The existence of an extrarenal factor(s) correcting the intrinsic MHS kidney abnormality in vivo is suggested, as no differences were reported in kidney function of intact adult animals.
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PMID:Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain at different ages. 659 80

Dantrolene sodium, a hydantoin analogue, is efficacious in the therapy of malignant hyperthermia (MH). In order to improve our knowledge of the mode of action of dantrolene, we have examined the influence of dantrolene sodium on: (1) twitch and resting tensions, in the absence and the presence of caffeine, of intact skeletal muscle fascicles; and (2) caffeine induced tension rises of single chemically skinned skeletal muscle fascicles. We have found that dantrolene appears to exert its beneficial action on malignant hyperthermia susceptible (MHS) skeletal muscle by an indirect action on the sarcoplasmic reticulum (SR). Thus dantrolene inhibits twitch tensions of skeletal muscle fascicles, probably by indirectly preventing the release of calcium from the SR. To a lesser extent dantrolene inhibits caffeine induced contractures of skeletal muscle fascicles, probably by indirectly accelerating the uptake of calcium into the SR. Because the former effect is greater than the latter in vivo dantrolene sodium is effective only when given prior to total loss of calcium from the SR. Vigilant temperature and EKG monitoring of all patients during anaesthesia is, therefore, essential.
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PMID:Dantrolene--in vitro studies in malignant hyperthermia susceptible (MHS) and normal skeletal muscle. 670 79

The effects of an induced malignant hyperthermia (MH) crisis have been studied in the intact pig. Both physiological and biochemical changes in skeletal muscle were studied. MH was induced with 3% halothane plus a bolus injection of succinylcholine. In the prechallenge period a significant difference was observed in the concentration of certain muscle metabolites, comparing the MH-susceptible (MH+) with the non-susceptible (MH-) pigs. A lower level was measured for phosphocreatine (PCr), inosine monophosphate (IMP) and an increased level of lactate and creatine (Cr) in the susceptible pigs (MH+). The challenge caused a significant reduction of the level of PCr and adenosine in MH+ pigs, compared to the prechallenge period. After administration of dantrolene sodium, a significant decrease was measured in the level of lactate, compared to the prechallenge period as well as during the challenge. In contrast, in the control pigs no significant changes were observed in muscle metabolites, either after induction of MH or after the administration of dantrolene sodium. Enzyme activity determinations of muscle adenylate kinase and adenosine monophosphate (AMP)-deaminase did not show any difference in activity either before or during the MH crisis or after treatment with dantrolene sodium. The earliest physiological change during an induced MH crisis in our study was the rapid increase of the end-tidal CO2. Within 5 min after MH induction, end-tidal CO2 was doubled. It is concluded that the monitoring of the end-tidal CO2 is essential to diagnose MH at a very early stage.
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PMID:In vivo induced malignant hyperthermia in pigs. I. Physiological and biochemical changes and the influence of dantrolene sodium. 671 Dec 53

Biceps femoris muscle biopsies of malignant hyperthermia susceptible (MH+) and non-susceptible (MH-) Dutch Landrace pigs were studied ultrastructurally, and exchangeable calcium was demonstrated, using the antimonate precipitation technique in combination with electron probe x-ray microanalysis. Biopsies were taken before and during the administration of halothane-plus-succinylcholine and after dantrolene sodium treatment of the animals. MH+ muscle, taken before the MH triggering, showed a high proportion (about 35%) of cells with supercontraction. Both MH+ and MH- muscle had broad but nearly identical ranges of cell diameter. Core-like structures were occasionally present in muscle from MH+ pigs. Muscle mitochondria from the MH+ pigs accumulated large amounts of calcium in their matrix compartment during the halothane-plus-succinylcholine induced MH crisis. This calcium loading in the course of time caused swelling and structural damage to the mitochondria. Skeletal muscle mitochondria from MH- pigs did not show such a reaction pattern on challenge with halothane and succinylcholine. It is concluded that in MH+ pigs the challenge brings about an increase in myoplasmic free calcium, which is predominantly due to calcium influx from the extracellular fluid. This rise in cytosolic calcium causes the mitochondria to accumulate the cation in an energy-dependent way. These findings are discussed in relation to the diverging halothane and caffeine contraction responses of aerobic type I and anaerobic type II muscle fibres.
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PMID:In vivo induced malignant hyperthermia in pigs. III. Localization of calcium in skeletal muscle mitochondria by means of electronmicroscopy and microprobe analysis. 671 Dec 59


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