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)

The biochemical characteristics of skeletal muscle mitochondria of malignant hyperthermia (MH) susceptible Dutch Landrace pigs have been investigated before and during an MH attack, induced in vivo by halothane plus succinylcholine. The muscle homogenates have a decreased capacity to synthesize ATP and creatine phosphate during the MH period. Muscle mitochondria prepared from susceptible pigs in an MH period consume less oxygen than do mitochondria isolated before the attack, or mitochondria from control pigs during the challenge. The oxidative phosphorylation is not uncoupled during the critical period. The production of CO2 indicates that the in vitro measured capacity of the MH muscle mitochondria correctly reflects the in vivo condition during the MH attack. The restricted synthesis may be caused by a factor, finding expression in the mitochondria themselves, and obtained or activated during the MH attack.
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PMID:In vivo induced malignant hyperthermia in pigs. II. Metabolism of skeletal muscle mitochondria. 671 Dec 68

Malignant hyperthermia (MH) may result from increased intracellular calcium concentrations. Increased 1,4,5-IP3 concentrations could mediate this increase in Ca2+. In this study we measured inositol polyphosphates in selectively bred MH susceptible (MHS) and MH non-susceptible (MHN) swine. MH crisis was induced by halothane challenge, and dantrolene was administered in order to measure inositol polyphosphates after MH reversal. Muscle biopsies of skeletal muscles of the hind limbs were obtained in random order and inositol polyphosphates determined by high pressure liquid chromatography using a metal dye detection method. Inositol polyphosphates were determined in three groups: (1) MHS vs MHN basal, (2) during MH crisis induced by halothane and (3) following treatment with dantrolene after halothane challenge. Clinical variables (P(_)VO2, P(-)VCO2, PE'CO2 and pH) indicated that MH was readily induced in MHS swine. Basal concentrations of all inositol polyphosphates were higher in MHS swine compared with MHN swine. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 concentrations increased in MHS animals compared with the respective baseline values, whereas no changes in MHN animals could be detected. Dantrolene administration decreased inositol polyphosphate concentrations in MHS swine. MHN swine showed no changes in inositol polyphosphates after dantrolene. These findings indicate that inositol polyphosphates may be involved in metabolic changes after triggering and treatment of MH.
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PMID:Alterations of inositol polyphosphates in skeletal muscle during porcine malignant hyperthermia. 748 90

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In humans, MH is inherited in an autosomal dominant fashion; in swine, the principal model for MH, it is in a recessive fashion. Those with MH susceptibility usually are asymptomatic except in the presence of certain "triggering" anaesthetic agents such as isoflurane, enflurane and the muscle relaxant succinylcholine. Upon such exposure hypermetabolism, increased CO2 production, acidosis, muscle rigidity, rhabdomyolysis and hyperthermia occur. Untreated, death may result in 70% of patients. With prompt diagnosis and treatment with dantrolene sodium, the mortality is less than 10%. The overall incidence of MH is low (perhaps 1:50,000 anaesthetics), but it is more common in children. Children also display a paradoxical increase in jaw muscle tone to succinylcholine which often presages MH, but confusing clinically, may also be a normal response to succinylcholine. The pathophysiology of MH centres around a defect in calcium flux in skeletal muscle. A specific base pair change in the gene that codes for the ryanodine receptor calcium channel in muscle has been demonstrated in susceptible swine, but occurs rarely in humans. It is hoped that the understanding of the molecular genetics of MH will lead to a simpler diagnostic test than is currently available, and enhance our understanding of MH and its relation to other myopathies.
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PMID:An update on the malignant hyperthermia syndrome. 771 Feb 42

One hundred and fifty paired extensor long digital muscles were excised from Wistar rats and each muscle was prepared in Krebs-Ringer's solution (K-R solution) then gassed with a mixture of 95% O2-5% CO2. The medium for the control muscles was replaced with K-R solution containing 10(-6) M ryanodine and that for the experimental muscles was replaced with medium containing 10(-6) M ryanodine and local anesthetic (LA) (procaine, tetracaine, benzocaine, lidocaine or bupivacaine at various concentration). Isometric contracture tension was recorded throughout the experiment. The ratios of the maximal contracture tension (C-ratio) and the elapsed time (T-ratio) of the muscles treated with LA compared to those of control muscles were calculated. Tetracaine (0.125-1.0 mM) specifically reduced the C-ratio. Procaine (0.5-1.0 mM) and tetracaine (10-60 microM) increased the T-ratio. Procaine (8-16 mM), benzocaine (4-8 mM), lidocaine (0.5-4 mM) and bupivacaine (0.125-1 mM) reduced the T-ratio. The influences of LAs on ryanodine-induced contracture could be explained in terms of their effects on the Ca(2+)-induced Ca2+ release mechanism, direct Ca2+ efflux from sarcoplasmic reticulum (SR), activity of Ca2+ uptake into SR and ryanodine-receptor binding. The complexity of LA effects on ryanodine-induced contracture will affect the results of ryanodine contracture tests for malignant hyperthermia when the muscle specimen is excised under local anesthesia.
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PMID:[The influences of local anesthetics on ryanodine-induced contracture in rat skeletal muscle]. 774 90

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

Since muscle relaxants have been implicated in triggering malignant hyperthermia (MH) in MH-susceptible humans and animals, the potential of new muscle relaxants for triggering MH needs to be assessed in vivo in MH-susceptible pigs. The triggering potential of atracurium was evaluated in six MH-susceptible pigs during one hour infusion of a 90% blocking dose (0.4 mg/kg/h) of atracurium. The mean recovery time (25% to 75%) was 10.2 min and a slight increase in heart rate (142 to 170 beats per minute) was observed. Rectal temperature decreased slightly (36.4 to 35.6 degrees C) and end tidal CO2 was stable at 5.46 kpa. In this study atracurium did not trigger MH in susceptible pigs.
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PMID:[Malignant hyperthermia in swine: a study of atracurium in MH-susceptible swine]. 814 61

A 53-year-old woman was scheduled for elective surgery of a L4-L5 lumbar disc prolapse. Preoperatively, she reported of a hereditary muscle disease in her family which could be identified as familial hyperkalaemic periodic paralysis. In patients with familial periodic paralysis, only limited information is available in the current anaesthesiological literature. This is especially true of the hyperkalaemic form which was separated from the hypokalaemic form in 1957. Most patients suffering from periodic paralysis will develop myotonic symptoms in time, but evidence is lacking that the incidence of malignant hyperthermia (MH) is higher than in normals. However, abnormalities of the electrocardiogram (ECG) due to changes in the potassium serum levels are not unusual, and the anaesthesiologist must be aware of cardiac arrhythmias. In the present case, the patient was anaesthetized using fentanyl, midazolam, and vecuronium, and ventilated with 66% nitrous oxide in oxygen. Radial artery blood pressure, end-tidal CO2, and nasopharyngeal temperature were monitored continuously. Surgery was completed after 2 hours with no abnormalities in the intraoperative course. Recovery from anaesthesia was uneventful. During the postoperative follow-up for 1 week, further attacks of paralysis, intermittent sodium-potassium imbalance of the muscle cell membrane appears to be the primary pathogenetic factor. In this special disease, prevention of carbohydrate depletion and the avoidance of muscle relaxants are recommended in the anaesthesiological literature. However, a specified regimen of general anaesthesia has not yet been outlined. In our special case, the use of anaesthetics deemed to be safe in MH susceptible patients produced an uneventful perioperative course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anesthesia in familial hyperkalemic periodic paralysis]. 832 4

A 6-year old female child received succinylcholine (1 mg.kg-1) and isoflurane (concentrations of 1.5-2 percent) and developed at the end of surgery a hypermetabolic syndrome suggestive of malignant hyperthermia (MH) with masseter muscle spasm, muscle rigidity, tachypnea, systolic hypertension (140 mm Hg), tachycardia (205 beats.min-1), hypercarbia (end expiratory CO2 71 mmHg), and an increase in body temperature (39.2 degrees C). The child responded well to therapy which included cooling, hyperventilation with pure oxygen and dantrolene administration. However, blood creatine kinase and myoglobin elevations were moderate (respectively 375 IU.L-1 and 114 micrograms.L-1) and an in vitro halothane and caffeine contracture test was negative. Differential diagnostic proposals are discussed and compared to the clinical incident.
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PMID:Malignant hyperthermia suggestive hypermetabolic syndrome at emergence from anesthesia. 871 51

The authors report on a course of malignant hyperthermia (MH) in an almost 5-years old boy. In the past, he had been anaesthetized two times with halothane without complications. The causative triggering agent was sevoflurane, a new user-friendly substance for paediatric anaesthesia. Forty five minutes after induction of anaesthesia he developed symptoms of a MH-crisis with increase in endexspiratory CO2 up 87 mmHg and followed by an increase in heart rate up to 160 beats/minute. The blood gas analysis showed a respiratory and metabolic acidosis. The timely administration of dantrolene rapidly reversed the life-threatening signs and prevent progression of the disease. It is apparent that monitoring of endtidal carbon dioxide by means of capnometry is of crucial importance in detecting MH at an early stage, and appropriate treatment is being instituted more promptly. By such early recognition, and treatment with dantrolene, we can reasonably except a further decrease in mortality and morbidity of this enigmatic disorder.
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PMID:[Malignant hyperthermia and sevoflurane--a case report]. 944 66

Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available.
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PMID:Malignant hyperthermia. 953 80


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