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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatine-phosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterised by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum.
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PMID:'Picture frame' fibres in a carrier of the trait for malignant hyperpyrexia. 0 Jul 95

This communication presents evidence in support of a neuropathic basis for the myopathy associated with malignant hyperpyrexia (MH). Muscle from MH susceptible individuals showed a reduced calcium uptake by the sarcoplasmic reticulum. There was a reduced concentration of phosphocreatine and ATP and an increased concentration of glucose-6-phosphate in these muscle samples.
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PMID:Morphological and biochemical defects in muscles of human carriers of the malignant hyperthermia syndrome. 12 80

The presence of denervation-like changes and abnormal mitochondria in the muscle of carriers of the malignant hyperthermia syndrome suggest a neuropathic basis for the human syndrome. A defect in mitochondrial ATP synthesis resulting from denervation, and potentiated by some general anaesthetics, may be the primary muscle fibre lesion in the human malignant hyperthermic syndrome.
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PMID:Malignant hyperthermia syndrome--evidence for denervation changes in human skeletal muscle. 13 24

Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)
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PMID:Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation. 16

MHS and normal pigs were anaesthetized with nitrous oxide and diazepam. Halothane 1% was then administered for 1 hr. Immediately before and immediately after the halothane inhalation, 10 g of vastus lateralis muscle was excised. SR was isolated from this muscle. Calcium accumulation by the MHS sarcoplasmic reticulum in the absence of halothane was greater than normal. Halothane in vitro produced a similar increase in calcium uptake into both the MHS and the normal SR. Halothane in vivo significantly reduced calcium accumulation by hyperthermic SR but had no significant effect on calcium uptake into the normal SR. Thus the action of halothane on the MHS sarcoplasmic reticulum is indirect, occurring only in the intact cell. It is possibly a result of the deleterious effect which lack of ATP, a low pH or a high temperature is likely to have on the calcium accumulating mechanism of the SR membrane. Our results suggest that the primary defects of porcine and human malignant hyperthermia are not entirely synonymous.
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PMID:Calcium uptake into muscle of pigs susceptible to malignant hyperthermia: in vitro and in vivo studies with and without halothane. 23 50

The muscular rigidity associated with anesthetically induced malignant hyperthermia has been attributed to an increase in myoplasmic free calcium concentration. However, previous in-vitro studies have shown that increased temperature can eliminate the calcium requirement for actin-myosin interaction. Therefore, the calcium dependency of human skeletal muscle actomyosin in response to temperature increases of the magnitude encountered in human muscle during hyperthermic episodes was investigated. Calcium dependency is expressed in terms of the ability of a calcium-chelating agent, EGTA, to inhibit the ATP-induced turbidity increase of actomyosin suspensions (superprecipitation). In the presence of millimolar concentrations of ATP and magnesium, EGTA completely inhibits superprecipitation at temperatures as high as 35 C. With further increase in temperature this inhibition is progressively reduced until, at 45 C, the extent of superprecipitation is independent of the calcium concentration. Loss of calcium control is potentiated by reduction in the ATP concentration. Since the muscular rigidity of malignant hyperthermia is associated with both an elevation of muscle temperature and a decline in muscle ATP content, it is evident that in this disorder conditions might exist for an increase in muscle tension that is independent of changes in intracellular free calcium concentration.
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PMID:Thermal inactivation of the calcium regulatory mechanism of human skeletal muscle actomyosin: a possible contributing factor in the rigidity of malignant hyperthermia. 80 55

Thirteen of 31 Belgian Landrace pigs developed malignant hyperthermia (MH) after breathing halothane. A short period of exercise 1 h before the administration of the triggering agent increased the incidence of the syndrome to 100% in eight similar pigs. Clinical symptoms were more marked and developed more rapidly in the exercised pigs. All the reacting pigs became typically acidotic, developed rigor and died. Serum Na+, K+, Ca2+, c.p.k., l.d.h. and protein concentrations were increased to a variable extent during the reaction and there was an increase in p.c.v. also. No hyperglycaemia was detected in pigs which were rested before receiving halothane. Four of the eight exercised pigs became markedly hyperglycaemic and plasma noradrenaline increased to higher values. Phosphocreatine and ATP decreased to low values and lactate increased in the muscles of all pigs which reacted. At the time of death, muscle glycogen had decreased significantly in the rested, but not in the exercised, MH pigs.
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PMID:Malignant hyperthermia in Belgian Landrace pigs rested or exercised before exposure to halothane. 97 90

The adenosine triphosphate (ATP depletion ratio, which is the ratio [ATP] in skeletal muscle equilibrated with carbogen and 4% halothane for 30 minutes divided by [ATP] in skeletal muscle equilibrated with carbogen alone for 30 minutes is less than normal in most but not in all rigid MHS patients. The ratio is normal in non-rigid MHS patients. This diagnostic tool is, therefore, useful in the diagnosis of rigid MH. It is not, however, such a sensitive diagnostic parameter as the caffeine contracture test.
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PMID:The adenosine triphosphate (ATP) depletion test: comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility. 99 Sep 79

Effort rhabdomyolysis is a syndrome which takes the form of a pathology with different etiopathogenetic stages. General anesthesia may trigger off acute muscular cytolysis which is probably influenced by the inflammatory surgical pathology itself. The observation of two cases of post-anesthetic rhabdomyolysis following muscular stress suggest that the exhaustion of muscle energy reserves and the consequent alteration of the ATP/ADP ratio may act as a trigger mechanism for this syndrome. Its close relationship with malignant hyperthermia makes a precise anamnesis vitally important, especially in relation to recent intense physical effort in patients undergoing emergency surgery for acute pathologies.
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PMID:[Post-anesthesia rhabdomyolysis syndrome following muscular stress. 2 case reports]. 129 23

The sarcoplasmic reticulum (SR) controls uptake and release of Ca2+ in muscle. Little information is available regarding the effect of volatile anesthetics on Ca2+ release from SR isolated from normal skeletal muscle, even though an abnormality of Ca2+ handling is implicated in malignant hyperthermia. In this study we used a Ca2+ electrode to monitor continuously the release of Ca2+ from SR and the effect of volatile anesthetics on this process. We found that halothane, enflurane, and isoflurane at 0.6, 0.7, and 0.8 vol%, respectively, each increased the velocity of Ca2+ leakage by at least 150% when compared to control. Ruthenium red, a blocker of the SR Ca(2+)-release channel, was shown to have no effect on the velocity of Ca2+ leakage. Halothane and isoflurane both shortened the time at which Ca2+ leakage began (T) in a dose-dependent fashion. Halothane at 4.8 vol% decreased T from 293 +/- 21 s to 149 +/- 20 s. Isoflurane (4.8 vol%) decreased T to 203 +/- 16 s, and enflurane at 5 vol% had little effect, decreasing T to 259 +/- 19 s. We noted a marked stimulation in the ATPase activity of the SR by all three volatile anesthetics. Halothane at 0.63 vol%, isoflurane at 0.42 vol%, and enflurane at 0.62 vol% each increased ATPase activity by at least 300%. We conclude that the stimulation of the velocity of Ca2+ leakage by the volatile anesthetics is related to the more rapid depletion of ATP, but that the shortening of the onset of Ca2+ leakage is a independent phenomenon with a markedly different dose dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Halothane, enflurane, and isoflurane stimulate calcium leakage from rabbit sarcoplasmic reticulum. 153 95


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