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)

Fura-2 was used to estimate myoplasmic [Ca2+] in intact fibers and fiber segments from normal and diseased human muscles. Small muscle bundles (20-50 fibers) were loaded with the membrane-permeant form of the dye (Fura-2 AM). High-performance liquid chromatography was utilized to study the ability of these cells to hydrolyze Fura-2 AM. Immediately after the 30 min loading period, Fura-2 (the Ca2+ indicator) was the predominant form of the dye in all preparations and the concentration within these fibers remained stable for over 4 1/2 hours. In addition, the resting myoplasmic [Ca2+] in fiber segments from normal subjects and those susceptible to malignant hyperthermia were the same. However, halothane administration (1.5%) induced correlated increases in myoplasmic [Ca2+] and force only in fibers from the susceptible patients. In contrast, caffeine administration causes correlated increases in myoplasmic [Ca2+] and force in both types of muscle, but lower concentrations were needed to do so in the fibers from the susceptible patients. The effects of halothane and caffeine were reversible. We conclude that Fura-2 can be used successfully to estimate resting levels and changes in myoplasmic [Ca2+] in human skeletal muscle.
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PMID:The use of Fura-2 to estimate myoplasmic [Ca2+] in human skeletal muscle. 272 Jul 59

Malignant hyperthermia (MH) is a seemingly rare genetic myopathy. Hypermetabolic crisis accompanied by a rise in body temperature to as high as 44 degrees C, is its hallmark. Malignant hyperthermia is usually triggered by potent inhalation anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary incidence of death in patients who are at risk, pediatric surgeons may be reluctant to operate on these patients. Eight such patients were referred to the Pediatric Surgery Service and the UCLA Malignant Hyperthermia Center following pediatric surgical procedures aborted for first episodes of malignant hyperthermia (five) or for a strong family history of malignant hyperthermia (three). They were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants. The patients were not treated prophylactically with dantrolene. Cardiac monitoring, end-tidal PCO2, and rectal temperatures were monitored. After completion of their pediatric surgical procedures, all eight patients had a vastus lateralis muscle biopsy performed and subsequent caffeine/halothane contracture studies completed. The contracture study result was positive in all patients studied. No anesthetic or surgical complications were encountered. This study shows that patients at risk for developing MH crisis can have pediatric surgical procedures performed safely with appropriately selected general anesthesia.
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PMID:Malignant hyperthermia: experience in the prospective management of eight children. 272 6

In the present report we described two cases of malignant hyperthermia under halothane anesthesia. Case 1; A 54-year-old, 58 kg-male was scheduled for the operation of giant arterio-venous malformation. Anesthesia was induced with thiamylal, fentanyl and pancuronium, and maintained with oxygen, nitrous oxide and halothane. The patient was subjected to halothane inhalation for 26 hours prior to the development of the malignant hyperthermia. Although body temperature rose to 41 degrees C, it returned to normal with the administration of 280 mg of dantrolene and systemic cooling. Case 2; A 31-year-old, 68 kg-female was scheduled for tonsillectomy. Anesthesia was induced with thiamylal, oxygen, nitrous oxide and halothane. After the administration of 70 mg of SCC, marked muscular rigidity occurred and endotracheal intubation was impossible. The operation was postponed. Two months after the first anesthesia, operation was successfully performed under NLA with droperidol and fentanyl. Caffeine contracture test was performed in each case by skinned fiber method and the result showed that the sensitivity to caffeine increased in the isolated skeletal muscle fiber bundles from these patients. Thresholds of caffeine contracture of these skinned fiber bundles were all lower than 5mM caffeine.
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PMID:[Malignant hyperthermia; two cases of MH in the presence of general anesthesia and performing caffeine contracture test]. 272 20

To evaluate the reliability of the in vitro contracture test for susceptibility to malignant hyperthermia, we studied muscles from normal pigs and those susceptible to malignant hyperthermia. We performed the contracture test with various muscles from the same animal. Trapezius and intercostal muscles gave similar results, whereas the extensor digiti II muscle had lower sensitivities to both caffeine and halothane. Thus, the muscle chosen to determine susceptibility to malignant hyperthermia is important. In several animals, a false negative diagnosis would have resulted if only the distal muscle had been studied, and this was true even if weak contractures (less than 200 mg) were considered significant. In addition, we compared the response to caffeine or halothane of cut and intact muscle fibers. Although the cut fibers were depolarized, the sensitivity to these drugs was unchanged. Hence, results of the in vitro contracture test are independent of the resting membrane potential.
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PMID:The in vitro determination of susceptibility to malignant hyperthermia. 272 48

We have carried out a comparative study of caffeine sensitivity of the sarcoplasmic reticulum (SR) of fast and slow normal human fibers chemically skinned. Human slow-fiber SR is more sensitive to caffeine than fast fiber SR; however, it releases less calcium and at a lower rate than the SR of fast fibers when exposed to threshold concentrations of caffeine. These results indicate that the SR calcium release mechanisms of SR of fast and slow human fibers are homologous but not identical. An increased sensitivity of SR to caffeine is found in both fast and slow fibers from human malignant hyperthermia muscle. However, fast fibers seem to be the most affected, since their caffeine threshold for contraction is very close to that of slow fibers.
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PMID:Caffeine sensitivity of sarcoplasmic reticulum of fast and slow fibers from normal and malignant hyperthermia human muscle. 272 62

31Phosphorus-NMR spectroscopy may have the potential to help in the noninvasive diagnosis of malignant hyperpyrexia (MH). Changes in the phosphate-metabolite profile of MH-susceptible (MHS) skeletal muscle occur more readily under conditions of anoxia than in control muscle. Induction of anoxia caused a rapid fall in intracellular phosphocreatine, an elevation of inorganic phosphate, and finally a diminution of ATP in MHS muscle. The onset of metabolic change was slower in control tissue. Increased oxygen consumption may occur in anoxic MHS muscle, which leads to accelerated glycolysis and a rapid fall in the intracellular high-energy phosphates. In MHS muscle an abnormality may exist in carbohydrate metabolism linked with poor resynthesis of the high-energy phosphates, which may be precipitated under anaerobic conditions. Accelerated muscle metabolism is also observed in the presence of 2 mM caffeine and 3% halothane in MHS muscle. Changes in the concentrations of metabolites could be mapped noninvasively under anoxic conditions using topical 31P-NMR.
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PMID:31P-NMR spectroscopy: the metabolic profile of malignant hyperpyrexic porcine skeletal muscle. 272 66

Porcine skeletal muscle fibers were studied to determine if the defect in malignant hyperthermia involves transverse tubule (TT) to sarcoplasmic reticulum (SR) communication. Peeled (mechanically skinned) skeletal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs were stimulated with Cl- to ionically depolarize transverse tubules and thereby trigger Ca2+ release from SR. Caffeine was used to directly stimulate the Ca2+-induced Ca2+ release mechanism (CaIR) of the sarcoplasmic reticulum. Calcium released from internal fiber stores was monitored as Ca2+-activated isomeric force generation in the form of tension transients. Cl- -induced tension transients result from a primary component of Ca2+ release which triggers a secondary CaIR component; CaIR and caffeine contractures were eliminated by procaine. The primary component of Cl- -induced SR Ca2+ release was indistinguishable for MHS and normal skeletal peeled fibers at all TT resting and Cl- stimulation conditions. Only the magnitude of the secondary CaIR component was significantly larger in MHS fibers. The [Ca2+] threshold for secondary CaIR was lowered by resting TT depolarization in both normal and MHS fibers. Conditions for resting TT hyperpolarization selectively reduced the magnitude of the secondary CaIR component of MHS fibers, making them indistinguishable from normal.
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PMID:Skeletal muscle excitation-contraction coupling. I. Transverse tubule control of peeled fiber Ca2+-induced Ca2+ release in normal and malignant hyperthermic muscles. 272 33

The effects of two structurally similar butyrophenones (droperidol and haloperidol) and ketamine were evaluated in an in vitro system to determine their potential for eliciting or exacerbating an episode of malignant hyperthermia. Muscle strips from patients referred for diagnostic testing for malignant hyperthermia and muscle strips from the rat diaphragm were exposed to droperidol, haloperidol, or ketamine prior to challenge with halothane, succinylcholine or caffeine. If any agent augmented the contracture response to the malignant hyperthermia triggering or diagnostic agents, then the agent was considered unsafe for use in malignant hyperthermia susceptible patients. Droperidol 10 mumol/l and ketamine 100 mumol/l did not induce contractures in human or rat skeletal muscle when added alone, nor did they augment halothane, succinylcholine or caffeine contractures. These agents appear to be safe for use in patients susceptible to malignant hyperthermia. In contrast, haloperidol 10 mumol/l augmented the response to succinylcholine about 1.5-fold and may be contraindicated in MH susceptibles.
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PMID:Effects of droperidol, haloperidol and ketamine on halothane, succinylcholine and caffeine contractures: implications for malignant hyperthermia. 272 21

Diltiazem inhibited and antagonized the abnormal contractures induced by halothane, caffeine and potassium chloride in isolated skeletal muscle from pigs susceptible to malignant hyperpyrexia (MHS). Contractile responses to caffeine and electrical stimulation also were suppressed by diltiazem in control tissue. Similar effects were obtained in the presence of dantrolene. In both MHS and control preparations, diltiazem antagonized caffeine-induced contractures in the presence of maximal effective concentrations of dantrolene, and the converse was true also. In MHS and control preparations detubulated by glycerol, diltiazem did not inhibit or antagonize caffeine-induced contractures while dantrolene did. Diltiazem seems to modify contractile responses at the level of the transverse tubule membrane by inhibiting the inward flow of extracellular Ca2+, while dantrolene inhibits Ca2+ release directly from the sarcoplasmic reticulum. Ca2+ influx through transverse tubules may be important in the aetiology of the MH syndrome.
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PMID:Effect of diltiazem and dantrolene on the contractility of isolated malignant hyperpyrexia-susceptible porcine skeletal muscle. 273 Aug 30

Malignant hyperthermia (MH) diagnostic biopsy centers across North America have not previously been standardized in regard to protocols and specific muscles. Recent standardization criteria prompted this study of the vastus and rectus abdominis muscles. This study evaluated changes in contracture tension after electrical stimulation of 271 bundles taken from the vastus (n = 16) and rectus abdominus (n = 19) muscle biopsies of normal individuals when exposed to tissue baths in the absence of and in the presence of caffeine (0.5, 1.0, 2.0, 4.0, 8.0, and 32.0 mM) alone, halothane (1% or 3%) alone, or the combination of halothane (1%) plus caffeine (0.25, 0.5, 1.0, 2.0, 4.0, and 32.0). Caffeine threshold concentration was that concentration of caffeine that produced a 7% increase in tension. Caffeine specific concentration (CSC) and halothane caffeine specific concentration (HCSC) were those concentrations of caffeine alone or of halothane plus caffeine that produced a 1 g increase in tension. The concentration of caffeine alone that increased the contracture tension by 7% averaged 6.7 +/- 0.3 mM for vastus, significantly greater than 4.1 +/- 0.2 mM for the rectus muscle biopsies. Caffeine specific concentration was significantly greater for vastus muscle (7.7 +/- 0.7 mM) than it was for rectus muscle (4.9 +/- 0.4 mM). Three percent halothane alone showed contractures in 3/41 vastus (all less than 0.5 g) and 18/54 rectus muscle bundles (8 greater than 0.5 g). Mean HCSC was statistically significantly greater for vastus muscle (1.9 +/- 0.2 mM) than for rectus muscle (1.2 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hyperthermia in humans--standardization of contracture testing protocol. 278 43


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