Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strandard laboratory rabbits which are not genetically susceptible to malignant hyperpyrexia were anesthetized with either halothane or pentobarbital. Administration of caffeine in 125 mg increments produced a syndrome strongly resembling malignant hyperpyrexia in rabbits anesthetized with halothane. All these animals became rigid, hyperpyrexic, acidotic and hyperkalemic, whereas caffeine-treated, pentobarbital-anesthetized animals developed only mild acidosis. Pentobarbital alone and halothane alone caused no changes in measured variables. This model for malignant hyperpyrexia resembles the naturally occurring disease more closely than several preceding pharmacologic models.
 ...
PMID:A laboratory animal model for malignant hyperpyrexia. 3 78

Clinical concentrations of anesthetics augment caffeine-induced contracture of frog sartorius muscle; however, anesthetics differ in this characteristic. The potentiation was quantitated using six paired sartorius muscles for each specified concentration of anesthetic and controls. At a concentration of 1 MAC, the greatest potentiation occurred with 2 mM caffeine for all anesthetics studied. Under these conditions the order of magnitude of augmentations was: chloroform (15 times); halothane (11 times); methoxyflurane (10 times); cyclopropane (5 times); enflurane (4 times); isoflurane (3 times); diethyl ether (2 times); Baxter 3224 (2 times); fluroxene (1.4 times); nitrous oxide (1.3 times). Halothane at .5 MAC augments the 2 mM caffeine-induced contracture almost seven times, and at 2 MAC almost 13 times, whereas 2 MAC isoflurane potentiates the caffeine-induced contracture only four times and 4 MAC diethyl ether only two and a half times. It is postulated that those anesthetics that most potentiate caffeine-induced contracture may be the most potent triggering agents of malignant hyperthermia.
 ...
PMID:An in-vitro model of malignant hyperthermia: differential effects of inhalation anesthetics on caffeine-induced muscle contractures. 30 36

In vitro muscle contracture responses in swine susceptible to malignant hyperpyrexia (MH) were similar to those found in muscle from humans susceptible to this anaesthetic complication, confirming the suitability of the pig as an animal model for studying MH. The results suggest that there are different degrees of susceptibility to MH. Whichever drug was used, there was some overlap in the contracture responses between susceptible animals and controls, suggesting that the most accurate way of identifying susceptibility to MH is to use a variety of chemical agents, the best of which seem to be halothane, caffeine, suxamethonium and potassium chloride. Thymol, which is used as a preservative in commercial preparations of halothane, potentiates halothane contractures, but it is not known if this is significant clinically.
 ...
PMID:Identification of susceptibility to malignant hyperpyrexia in swine. 43 38

Suxamethonium induced a contracture in caffeine pretreated human muscle in vitro. The contracture was significantly greater (P less than 0.001) with MHS muscle compared with muscle from normal subjects. This reaction is now used as an additional screening test for the MHS phenotype. The contracture was prevented by pretreatment with dantrolene.
 ...
PMID:A screening test for the malignant hyperpyrexia phenotype using suxamethonium-induced contracture of muscle treated with caffeine and its inhibition by dantrolene. 49 72

A therapeutic and prophylactic dose of dantrolene administered to malignant hyperthermia-susceptible pigs had no effect on the abnormal in vitro contracture response of subsequent muscle biopsies. The in vitro contracture response of MHS pig muscle to halothane and to caffeine was not altered by prior dantrolene treatment. It is concluded that prior dantrolene administration has no effect on the discrimination of porcine MSH by in vitro pharmacological testing.
 ...
PMID:Does prior dantrolene affect the in vitro diagnosis of malignant hyperthermia susceptibility? 52 74

A case of possible malignant hyperthermia in a 6-month-old child is presented. Malignant hyperthermia was manifested in this patient by persistent metabolic acidosis in the intraoperative and postoperative periods, by a rapid rise in temperature with concomitant unresponsiveness in the postoperative period, and by a positive caffeine-halothane stimulation test. The malignant hyperthermia occurring in the postoperative period resolved promptly following administration of dantrolene sodium. An unusual aspect of this case is that both of the child's parents had normal CPK values and negative caffeine-halothane stimulation tests.
 ...
PMID:Management of suspected malignant hyperpyrexia in an infant. 57 Dec 20

This study compares several methods for diagnosing susceptibility to malignant hyperthermia, using two groups of Poland China swine narrowly defined as genetically susceptible or normal (five pigs each) depending respectively on their response to halothane or to halothane and succinylcholine. Vastus medialis muscle biopsies were excised under thiopental-N2O-O2 anesthesia and used for examination of (1) contracture responses to halothane, (2) contracture responses to caffeine and halothane-caffeine, and (3) adenosine triphosphate (ATP) depletion with and without halothane. All studies were performed in organ baths at 37 C. Halothane alone produced contractures in two susceptible and one normal preparation; caffeine always produced a contracture at lower concentrations in susceptible muscle; caffeine-halothane contractures in susceptible muscle occurred at lower mean caffeine concentrations, but there was some overlap of individual values; mean ATP depletion was greater in susceptible muscle, but with considerable overlap. Comparisons with the findings of others were hampered by use of absolute rather than comparative values for tension, e.g., grams, rather than grams per cross-sectional area or fraction of peak tension. Examination of the complete dose-response curve provided the best comparative information and caffeine was the consistent predictor of susceptibility.
 ...
PMID:Muscle contractures and adenosine triphosphate depletion in porcine malignant hyperthermia. 57 59

Malignant hyperpyrexia is a dangerous complication of general anesthesia occurring in individuals with an underlying disease of muscle. The essential clinical features of the syndrome are a drastic and sustained rise in body temperature, metabolic acidosis, and widespread muscular rigidity. The results of experiments on susceptible pigs and in vitro studies of human muscle have shown that all the clinical features of the syndrome can be explained by a raised level of calcium ions in the myoplasm. This is caused by a massive and sudden release of calcium into the myoplasm from the calcium-storing membranes in the muscle cell when exposed to general anesthetic agents. Two myopathies predisposing to malignant hyperpyrexia have been identified. One is usually subclinical, dominantly inherited, and manifested only by raised serum CPK levels. The other occurs in young boys with a number of physical abnormalities, whose relatives are unaffected. The serum CPK is a useful screening test in families in which malignant hyperpyrexia has occurred. Unfortunately, though, the serum CPK is not a specific test, and in doubtful cases the only unequivocal method of establishing susceptibility to malignant hyperpyrexia is to carry out an in vitro muscle test in which the muscle is exposed to caffeine, halothane, succinylcholine, and potassium chloride. Susceptible individuals should be given local, regional, or spinal anesthesia if an operation is needed. If this form of anesthesia is unsuitable, barbiturates such as thiopentone, tranquilizers such as diazepam, narcotics such as Pantopon, and neuroanaleptics such as fentanyl, nitrous oxide, d-tubocurarine, and althesin appear to be safe. By far the most important aspect of treatment is prophylaxis. Early diagnosis and immediate cessation of the offending anesthetic agents are the most important factors in trying to reduce the very high mortality of the syndrome.
 ...
PMID:Malignant hyperpyrexia. 77 64

Skeletal muscle from normal human subjects produced linear contracture responses in vitro to caffeine at concentrations of between 4 and 32 mmol/litre. In the presence of 0.4% halothane, caffeine contractures were greater but the magnitude of halothane potentiation decreased as the caffeine concentration was increased. The contractures produced by caffeine 4 and 8 mmol/litre at 37 degrees C were significantly reduced by decreasing the temperature of the incubation solution to 25 degrees C. Among 57 normal subjects, 18% had fibres which responded to halothane treatment with contracture. On the basis of these findings, it is suggested that screening for malignant hyperpyrexia by in vitro pharmacological testing of skeletal muscle should be carried out at 37 degrees C, and should include exposure of the sample to halothane, caffeine, suxamethonium and potassium rather than to halothane alone.
 ...
PMID:Screening for malignant hyperpyrexia. 83 48

1. The effects of dantrolene on pharmacologically-induced contractures and potentiated isometric twitches in normal human skeletal muscle have been studied in vitro. 2. Dantrolene sodium, at concentrations of 3 mumol/l or less, attenuates basal twitch, inhibits halothane potentiation of basal twitch and inhibits halothane-potentiated potassium contractures, but has less effect on twitch potentiation by 2 mmol/l caffeine. 3. Caffeine contractures are attenuated by dantrolene concentrations of 12 mumol/l or greater. The effect of dantrolene on caffeine contracture is characterized by decreased contracture tension and by prolonged time to peak contracture. 4. The results indicate that halothane and 2 mmol/l caffeine have agonistic effects on the excitation-contraction (E-C) coupling mechanism, and suggest that they may act at separate E-C coupling sites. The relationships of these findings to the pathopharmacology of malignant hyperpyrexia are discussed.
 ...
PMID:Studies on normal human skeletal muscle in relation to the pathopharmacology of malignant hyperpyrexia. 89 Oct 45


1 2 3 4 5 6 7 8 9 10 Next >>