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)

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

Membraneous phospholipids of subcellular structures were determined from the musculature of German Landrace pigs of the GDR, following exposure to halothane. Mating variants A (H+ male X H+ female), B (H+ male X H- female), and C (H- male X H+ female) were used for positive responders (MHS), while variants B, C, and D (H- male X H- female) were used for negative responders (MHN). Four phospholipid fractions were recorded from the muscle samples for mitochondria and microsomes (according to SR section). Differences between the MHS and MHN groups for the above fractions and without consideration of mating variants and genotype were not observed, although unambiguous responses were exhibited by all animals, either positive or negative to halothan. Significant differences with regard to the above phospholipid fractions were recordable only for variant A (MHS group) as compared to D (MHN), in other words, for the homozygous genotypes, once the above results had been rearranged within MHS and MHN along with different mating variants and genotypes. However, no unambiguous results were obtainable for the heterozygous genotypes of mating variants B and C. Possible underlying reasons are discussed in some detail. The results obtained from mating variants A and D are likely to confirm earlier findings and seem to suggest that the sarcoplasmic reticulum is the primary site of origin of susceptibility to halothane or malignant hyperthermia.
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PMID:[Phospholipid content of subcellular structures in skeletal muscles after halothane loading in Landrace swine in relation to mating variants and genotype]. 277 27

A comparison was made of the physicochemical characteristics of erythrocyte membranes in two strains of spontaneously hypertensive rats, namely SHR and MHS and in patients with essential hypertension (EH). The authors confirmed the results of the previously reported studies that Na+/Li+/H+ countertransport rates were higher in the erythrocytes of patients with EH. The high rate of L1+ sodium-independent efflux hindered identification of Na+/H+ turnover in the rat erythrocytes. Na+/H+ turnover rate was higher in SHR and unchanged MHS rat erythrocytes. The rate of Na+/K+ countertransport was increased by 30-50% in SHR rats and by 90-110% in MHS rats as compared with control animals of respective lines. No difference was found in this parameter in EH patients. The erythrocytes from EH patients and SHR rats showed a higher sensitivity of their K+ channels to elevated intracellular calcium levels. This parameter was unaltered in MHS rats. In the red cells of MHS rats there was a 4-5-fold increase in hemolysis which was induced by higher intracellular calcium concentrations, which was associated with increased activity of a Ca2+-dependent form of protease. The level of Ca2+-induced hemolysis remained unchanged in the erythrocytes from SHR rats and EH patients. It has been concluded that, in terms of membrane abnormalities, in SHR rats are the most adequate model of human essential hypertension than are MHS rats.
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PMID:[Cation transport and calcium-induced hemolysis in the erythrocytes of patients with hypertension and in spontaneously hypertensive rats (comparative analysis)]. 281 Oct 49

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

In Quin-2-loaded erythrocytes of two genetically hypertensive rat strains (spontaneously hypertensive rats, SHR, and the Milan hypertensive strain, MHS) intracellular Ca2+ (Ca2+i) concentration and 45Ca influx rate were increased by 25-30 and 15-20% respectively, in comparison with normotensive controls (Wistar-Kyoto rats, WKY, and rats of the Milan normotensive strain, MNS). After 4 h incubation in the presence of 5 mmol/l sodium vanadate (Na3VO4) as an inhibitor of Ca-ATPase, 45Ca content of intact erythrocytes of SHR was twofold higher while erythrocyte count of stroke-prone SHR (SHRSP) was threefold higher than in WKY. This increase was observed in SHR during the pre-hypertensive stage. Under the same conditions, no difference was noted between MHS and MNS rats. The rate of 32P influx, as well as the concentration of exchangeable chloride, was studied. We failed to detect any significant differences in either parameter between hypertensive and normotensive rats, suggesting that altered cell membrane potential was not responsible for allied Ca fluxes. Erythrocyte shrinking, however, resulted in a two to threefold increase in the rate of 45Ca influx. Neither the rate of 45Ca influx nor Ca2+i were modified by the inhibitor of calmodulin-dependent reactions, R24571 (10 mumol/l). It is suggested that the higher rate of Ca2+ influx in Quin-2-loaded erythrocytes of SHR, as well as the increment in 45Ca content in intact erythrocytes treated with orthovanadate, is due to a change in membrane skeleton organization and cell shrinkage.
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PMID:Calcium transport in erythrocytes of rats with spontaneous hypertension. 284 88

Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH.
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PMID:Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia. 289 65

Stress has been suggested as a factor involved in the development of a malignant hyperthermia (MH) reaction. This study has compared the hormonal response of a group of patients susceptible to MH (MHS), with that of a control group, during diagnostic muscle biopsy under general anaesthesia. Preoperative adrenal cortical reserve was assessed using the Short Synacthen Test (SST). There was no significant difference between the groups in their hormonal response to the procedure, both groups showing a peroperative reduction in plasma cortisol concentration from an initially high value, and the SST was within accepted normal limits for both groups. It was concluded that patients susceptible to MH have normal adrenal cortical reserve and responded normally to the psychological and surgical stress encountered during this study.
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PMID:Adrenal cortical reserve in patients undergoing muscle biopsy for malignant hyperthermia screening. 291 13

To investigate possible abnormalities in erythrocyte membrane enzyme activities in the pharmacogenetic disorder MH, membrane ATPase activities have been examined in erythrocyte ghosts prepared from red blood cells of MHS and normal swine. While no differences were noted in Mg2+-ATPase activities, the (Na+, K+)-ATPase activity of MHS erythrocyte ghosts was less than that of normal ghosts. Ca2+-ATPase activity exhibited low- and high-affinity Ca2+-binding sites in both types of erythrocyte ghost. While the Km for Ca2+ was greater for normal than for MHS erythrocyte ghosts at the high-affinity Ca2+-binding site, the reverse was true at the low-affinity Ca2+-binding site. Irrespective of the type of calcium binding site occupied, the Vmax for normal erythrocyte ghost Ca2+-ATPase activity was greater than that for MHS ghosts. In the presence of calmodulin, there was now no difference between MHS and normal erythrocyte ghosts in either the Km for Ca2+ or the Vmax of the Ca2+-ATPase activity. To determine if the calcium pumping activity of intact MHS and normal pig erythrocytes differed, calcium efflux from the 45Ca-loaded erythrocytes was determined; this activity was significantly greater for MHS than for normal erythrocytes. Thus, the present study confirms that there are abnormalities in the membranes of MHS pig red blood cells. However, we conclude that these abnormalities are unlikely to result in an impaired ability of MHS erythrocytes to regulate their cytosolic Ca2+ concentration.
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PMID:Erythrocyte membrane ATPase and calcium pumping activities in porcine malignant hyperthermia. 296 54

In mature red cells of rats from Milan Normal (MNS) and Hypertensive Strains (MHS), the soluble Ca2+-dependent neutral proteinase (calpain) is present in similar amounts as the form requiring 0.1-0.2 mM Ca2+ for maximum catalytic activity. The amount of the endogenous calpain inhibitor, however, differs greatly in the red cells of the two strains. In red cells from hypertensive rats the activity of the inhibitor is 10 times less with a ratio of inhibitor to calpain activity (unit/unit) of 0.2; compared to red cells from normal rats, in which this ratio is approximately 2. This is the first demonstration of the existence, in a mammalian cell, of such a low ratio of calpain to inhibitor and implies the occurrence of a potentially "unregulated" intracellular soluble proteinase. This abnormal condition may be responsible for some of the structural and metabolic changes reported in rats of the genetically determined MHS strain.
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PMID:Decreased level of calpain inhibitor activity in red blood cells from Milan hypertensive rats. 301 42

In mature red cells of rats from Milan normal (MNS) and hypertensive strains (MHS), the soluble Ca2+ dependent neutral proteinase (calpain) is present in similar amounts with identical Mr of 110 kDa and a dimeric structure composed of two unequal subunits of Mr of 84 and 26 kDa. Conversely, the amount of the endogenous inhibitor is now confirmed by analysis of the specific activity to be approximately 10 times less in red cells of MHS rats. The inhibitor is present in red cells of both strains in three different oligomeric forms of Mr of 240, 120 and 64 kDa. This last molecular species corresponds to the single basic constituent subunit which is the reacting inhibitor form. The apparent equilibrium between the three oligomeric structures is Ca2+-dependent. The high (0.1 mM) Ca2+ requirement for the activity of calpain from erythrocytes of both strains is reduced to 1-5 microM in the presence of plasma membrane phospholipids. Activation of the enzyme in these conditions is prevented by the natural inhibitor. These results strongly support and further emphasize the hypothesis that the structural and functional abnormalities in MHS rats red cells result from an impairment in the modulation of intracellular calpain activity by interaction with its endogenous inhibitor.
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PMID:Characterization of the defective calpain-endogenous calpain inhibitor system in erythrocytes from Milan hypertensive rats. 302 Nov 28


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