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)

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 27 patients according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of propranolol 80 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 12), and were not affected by propranolol. In contrast, propranolol shifted the caffeine dose-response curve to the right and significantly increased the caffeine threshold in the MHS group. Propranolol did not influence the caffeine results in the normal response group group (n = 12). It is concluded that beta-blockers should be discontinued before investigation for MH susceptibility.
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PMID:Influence of propranolol on the in vitro response to caffeine and halothane in malignant hyperthermia-susceptible muscle. 280 Sep 78

Though a malignant hyperthermia (MH) crisis is still a critical event during general anesthesia, recent developments in prophylaxis and treatment should help in avoiding fatal episodes. The best means to avoid MH episodes would be early recognition of MH susceptibility. Today the only reliable test to identify MH susceptibility is the in vitro contracture test. Thus, to diagnose MH susceptibility we performed this test on muscle biopsies from 26 individuals who: (1) had an event during general anesthesia that may have been indicative of MH (4 patients); (2) had a family member with a medical history of MH (20 patients); or (3) had unexplained elevated CK levels (1 patient). The criteria according to which patients were submitted to the testing are shown in detail in Table 1. We used the standardized version of the contracture test that has been proposed by the European Malignant Hyperpyrexia Group. Muscle biopsies (20-30 mm long, 8 mm diameter) were dissected into 8-10 small bundles (2-3 mm diameter) and tested within 3 h post-biopsy in four independent tissue baths with various concentrations of caffeine or halothane. According to the concentration of caffeine or halothane necessary to elicit contractures exceeding a predefined force threshold (20 mN), it was possible to classify the patients as MHS (MH-susceptible), MHE (equivocal), or MHN (negative). In addition to the in vitro test, clinical, laboratory, and neurophysiological data were collected from these patients and correlated with the individual test results (Table 2). Thirteen patients were classified as MHS, five were MHE, and seven patients MHN (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Diagnosis of susceptibility to malignant hyperthermia using the in vitro contracture test]. 283 Aug 5

To further define the possible involvement of sarcoplasmic reticulum calcium accumulation and release in the skeletal muscle disorder malignant hyperthermia (MH), we have examined various properties of sarcoplasmic reticulum fractions isolated from normal and MH-susceptible pig muscle. A sarcoplasmic reticulum preparation enriched in vesicles derived from the terminal cisternae, was further fractionated on discontinuous sucrose density gradients (Meissner, G. (1984) J. Biol. Chem. 259, 2365-2374). The resultant MH-susceptible and normal sarcoplasmic reticulum fractions, designated F0-F4, did not differ in yield, cholesterol and phospholipid content, or nitrendipine binding capacity. Calcium accumulation (0.27 mumol Ca/mg per min at 22 degrees C), Ca2+-ATPase activity (0.98 mumol Pi/mg per min at 22 degrees C), and calsequestrin content were also similar for MH-susceptible and normal sarcoplasmic reticulum fraction F3. To examine sarcoplasmic reticulum calcium release, fraction F3 vesicles were passively loaded with 45Ca (approx. 40 nmol Ca/mg), and rapidly diluted into a medium of defined Ca2+ concentration. Upon dilution into 1 microM Ca2+, the extent of Ca2+-dependent calcium release measured after 5 s was significantly greater for MH-susceptible than for normal sarcoplasmic reticulum, 65.9 +/- 2.8% vs. 47.7 +/- 3.9% of the loaded calcium, respectively. The C1/2 for Ca2+ stimulation of this calcium release (5 s value) from MH-susceptible sarcoplasmic reticulum also appeared to be shifted towards a higher Ca2+-sensitivity when compared to normal sarcoplasmic reticulum. Dantrolene had no effect on calcium release from fraction F3, however, halothane (0.1-0.5 mM) increased the extent of calcium release (5 s) similarly in both MH-susceptible and normal sarcoplasmic reticulum. Furthermore, Mg2+ was less effective at inhibiting, while ATP and caffeine were more effective in stimulating, this Ca2+-dependent release of calcium from MH-susceptible, when compared to normal sarcoplasmic reticulum. Our results demonstrate that while sarcoplasmic reticulum calcium-accumulation appears unaffected in MH, aspect(s) of the sarcoplasmic reticulum Ca2+-induced calcium release mechanism are altered. Although the role of the Ca2+-induced calcium release mechanism of sarcoplasmic reticulum in situ is not yet clear, our results suggest that an abnormality in the regulation of sarcoplasmic reticulum calcium release may play an important role in the MH syndrome.
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PMID:Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle. 287 89

The cytoplasmic concentration of ionised calcium, [Ca2+]i, is believed to be altered by agents that induce a malignant hyperthermia (MH) crisis in susceptible individuals. MH patients were identified by the halothane and halothane/caffeine contracture tests done in isolated muscle biopsy specimens. [Ca2+]i was measured in isolated peripheral blood mononuclear cells from MH patients and controls by means of the fluorescent calcium ion indicator quin2. In the absence of halothane there was no significant difference in [Ca2+]i in cells from normal and MH patients. Addition of halothane (4 microliter/ml) significantly increased [Ca2+]i in cells from MH patients but not in controls. The halothane-induced increase in [Ca2+]i required extracellular calcium ions. This is the first evidence of the mechanism of action of halothane in cells of MH patients; the differential effect of halothane on [Ca2+]i might constitute the basis for a non-invasive screening test for MH.
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PMID:Anaesthetic-induced increase in ionised calcium in blood mononuclear cells from malignant hyperthermia patients. 288 Oct 37

To provide information regarding the cause of the muscle rigidity in malignant hyperthermia-susceptible (MHS) pigs, the Ca-induced Ca-release mechanism of the sarcoplasmic reticulum (SR), the Ca uptake by the SR, and the Ca-activated tension production of the contractile system were examined in skinned skeletal muscle fibers from MHS and normal pigs. In muscles of MHS pigs, the rate of Ca-induced Ca release was significantly higher than in normal muscle. The potentiation effect on Ca-induced Ca release by halothane and caffeine did not differ appreciably between MHS and normal fibers. The rate of Ca uptake by the SR and the Ca sensitivity of the contractile system of MHS fibers were not different from those of normal fibers, and halothane in an anesthetic concentration exerted no effect on them. Dantrolene inhibited the Ca-induced Ca release at 38 degrees C. These results suggest that the principal cause of malignant hyperthermia (MH) in MHS pigs is due to the enhancement of the Ca-induced Ca-release mechanism of the SR of the skeletal muscle.
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PMID:Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle. 291 63

Malignant hyperthermia (MH) is a genetic disease in man and other animal species that predisposes to a catastrophic hypermetabolic syndrome that is triggered by certain anesthetic agents. A working hypothesis is that a defect in regulation of muscle cell calcium is the primary mechanism that initiates the MH syndrome. This paper reviews the evidence for a defect in muscle cell calcium as regulated by the sarcoplasmic reticulum membrane system. Skeletal muscle biopsied from MH man, pigs and dogs has abnormal in vitro contracture response to halothane and caffeine and these responses can be altered by lowering calcium content of the bathing solution and/or the muscle. Measurements of MH muscle cell Ca2+ by Ca2+-specific microelectrodes in vivo and fura-2 in vitro have demonstrated abnormal Ca2+ levels in resting and in caffeine-stimulated states. The SR membrane system is the primary calcium regulating organelle in skeletal muscle and a likely site for the defect in MH muscle. Two Ca2+ regulating functions of the SR have been explored in SR isolated from MH muscle. An abnormality of the 100K Ca2+-ATPase protein that functions to transport Ca2+ from myoplasm to inside the SR does not appear to be responsible for MH. The most probable defective site in the SR appears to be Ca2+ release channels and a Ca2+-induced Ca2+ release pathway has been shown to be abnormal in SR from MH human and pig muscle.
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PMID:SR function in malignant hyperthermia. 306 91

Since increased intracellular Ca2+ is believed to be the main factor causing skeletal muscle contracture in human and porcine malignant hyperthermia, the potential effects of the ionophore A23187, which enhances intracytoplasmic Ca2+, were investigated in Pietrain pig muscles. These effects were compared with those of caffeine, known to induce dose-dependent contracture in vitro in isolated muscle from human subjects with malignant hyperthermia. For this purpose, the mechanical and biochemical actions of caffeine and A23187 were tested in intercostal muscle biopsies from 10 normal pigs and 10 with malignant hyperthermia. The results show that A23187 allowed very clear differentiation between the muscles of normal and pathological animals. In view of the wide spectrum of drug sensitivity characterizing subjects with malignant hyperthermia, it is suggested that exposure to A23187 be added to the halothane and caffeine tests currently used to detect this disease.
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PMID:Comparative effects of the ionophore A23187 on the mechanical responses of muscle in normal Pietrain pigs and pigs with malignant hyperthermia. 308 9

The results are reported of the contracture test obtained by using the calcium ionophore A 23187 (Calcimycin) in two patients, the son (A) and the mother (B). The past history of patient A revealed the occurrence of an impending malignant hyperthermia crisis during induction of anaesthesia in 1975. The A 23187 contracture test confirmed the presence of the malignant hyperthermia trait in patient A, whose muscle biopsy had been submitted to the caffeine contracture test, according to Ellis' technique, and found to be positive in the presence of 1 mmol of caffeine in the tissue bath; the contracture test could not be completed with a halothane contracture test, due to the impaired viability of the muscle fibres obtained. On the reverse, the mother (patient B) was found to be negative to the tests applied: the caffeine contracture test, the halothane contracture test and the contracture test performed with the calcium ionophore A 23187. It is suggested the A 23187 contracture test be added to the contracture tests as defined by the European Malignant Hyperpyrexia Group. This test could be of great help in identifying the percentage of relatives of MHS ("malignant hyperthermia susceptible") patients found to be MHE ("malignant hyperthermia equivocal").
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PMID:[Contracture test with ionophore A 23187 for the diagnosis of malignant hyperthermia]. 308 80

Malignant hyperthermia 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 inhalated anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary risk of death in patients who are at risk, plastic surgeons may be reluctant to operate on these patients. Five such patients were referred to the Plastic Surgery Service and the UCLA Malignant Hyperthermia Center for anesthetic and surgical management following plastic surgical procedures aborted for first episodes of malignant hyperthermia. 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 followed. After completion of their plastic surgical procedures, all five patients had a vastus lateralis muscle biopsy performed and subsequent caffeine/halothane contracture studies completed. The contracture study was positive in all patients studied. No anesthetic or surgical complications were encountered. This study demonstrates that patients at risk of developing malignant hyperthermia crisis can have plastic surgical procedures performed safely while undergoing appropriately selected general anesthesia.
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PMID:Malignant hyperthermia in plastic surgery. 317 76

Sixty-two suspected crises of anaesthetic malignant hyperthermia (MH) were collected between 1969 and 1988 by a retrospective inquiry which lasted four years. 33 patients (53%) died whilst 29 survived. 20 cases were confirmed to be MH, either directly or indirectly by way of muscle biopsy and halothane and caffeine contracture tests carried out according to the European MH group protocol by two laboratories. This group included 11 of the deaths, one family member of whom, at least, is sensitive (MHS), 7 MHS survivors and 2 survivors too young to undergo muscle biopsy but belonging to MHS families. 21 cases were highly suspect of MH: 15 of the deaths which occurred in a typical way, and 6 patients of three different families who have suffered from anaesthetic deaths which, clinically, suggested MH. Another 15 were possible MH cases, all survivors, including one case of Steinert's disease and a brother of a case of central core disease. 2 cases were still being debated, because they had equivocal results for the caffeine test (MHEc); the last 4 had negative muscle biopsies and were excluded. 33 close relatives of the MH patients were diagnosed as MHS. 44 others were found to be free from the genetic predisposition. It was strongly recommended to yet 11 others that they carry the MHS card because they were MHEc. The clinical, surgical and anesthetic pictures were always as described in the literature. The anaesthetic protocols included inhalational agents in 90% of cases; these were combined with suxamethonium in 55% of cases. Dantrolene was only used in 32% of cases, and then at inadequate doses and very often too late; this probably explains the large number of treatment failures. The number of severe forms of MH was also very high in this series (70%). The need to increase the means of prevention and screening for MH in France is stressed.
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PMID:[Registration of peranesthetic cases of malignant hyperthermia in France. An update]. 322 47


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