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)

This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum.
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PMID:Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum. 374 67

Strips of soleus (100% type I) and gracilis (90% type II) muscle were obtained from anesthetized cats and mounted in organ baths filled with aerated Krebs-Ringer solution (37 degrees C). The contractile patterns in response to electrical stimulation (0.1 Hz, 25 V, 5 ms), caffeine, halothane, and caffeine in the presence of halothane were examined in the two fiber types. The ability of 25 microM dantrolene to alter the contractile patterns was also evaluated. In vitro contractile properties in response to electrical stimulation were similar to properties observed in situ, except that twitch tension in soleus muscle was significantly less in vitro than in situ. In the presence of halothane, type I soleus muscle developed a rapid contracture. The contracture was blocked by pretreatment with dantrolene and was reversed by addition of dantrolene at the peak of the response. Halothane-induced contractures were not observed at any time in type II gracilis. Type I soleus was also significantly more sensitive both to caffeine alone and to caffeine in the presence of halothane than was type II gracilis. In both fiber types, halothane increased the sensitivity of the muscles to caffeine. Dantrolene attenuated caffeine-induced contractures in both fiber types, but the attenuating effect was less in the presence of halothane. The findings of a halothane-induced contracture in the cat soleus and differential sensitivities of the two muscle fiber types to caffeine indicate that further studies in these two muscles may be useful for delineating the mechanisms inducing contracture in muscle from individuals susceptible to malignant hyperthermia.
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PMID:In vitro responses of cat skeletal muscle to halothane and caffeine. 398 Mar 55

This study examines in vitro the contractures induced by halothane and succinylcholine in skeletal muscle taken as biopsy specimens from 42 patients referred to the authors' laboratory for diagnosis of malignant hyperthermia (MH) susceptibility. In addition, possible differences between the response of preparations from these same patients with and without a history of masseter muscle rigidity following succinylcholine (SCh) administration were determined to investigate the in vitro relationship of masseter muscle rigidity to MH. Halothane 3%-induced contractures in preparations from MH susceptibles were similar, whether the group had a history of masseter muscle rigidity (1.15 +/- 0.18 g; n = 10) or not (1.02 +/- 0.21 g; n = 14). Halothane did not induce significant contractures in those diagnosed as normals. Succinylcholine alone did not elicit contractures from preparations derived from MH susceptibles or nonsusceptibles. Succinylcholine induced significant contractures in all preparations preexposed to halothane. Preparations from MH-negative patients with a history of masseter muscle rigidity were rendered sensitive to halothane (contractures of 1.17 +/- 0.30 g; n = 4) when SCh was present. In contrast, halothane added in the presence of SCh did not induce contractures to the same extent in preparations from MH-negative patients without a history of masseter muscle rigidity. This is the first reported in vitro method by which to examine the clinically troublesome interaction between SCh and halothane. This approach also may prove to be important in further investigations of the relationship between masseter muscle rigidity and MH.
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PMID:In vitro interaction between halothane and succinylcholine in human skeletal muscle: implications for malignant hyperthermia and masseter muscle rigidity. 402 68

Erythrocyte osmotic fragility was determined in 27 Pietrain swine which were susceptible to malignant hyperthermia (MH), 29 Yorkshire swine which were resistant to MH (controls), and 50 crossbred swine (Pietrain x Yorkshire), half of which were MH susceptible. Halothane challenge tests and blood creatine kinase activity were used as criteria for determining MH susceptibility. Mean values for osmotic fragility of erythrocytes in concentrations of NaCl between 60 and 120 mM were significantly different for the 3 groups (P less than 0.001). Hemolysis (50%) of erythrocytes occurred at NaCl concentrations of 90 mM for Pietrains, 85 mM for crossbreds, and 78 mM for controls. Increased fragility values occurred in 96% of the Pietrains, 3% of the controls, and 42% of crossbred swine that were halothane test-positive, and 58% of halothane test-negative crossbreds (P less than 0.05). The mean time of onset of signs of MH in response to halothane challenge testing was twice as long in the crossbreds as in Pietrains (P less than 0.01). Reticulocyte counts were moderately high in blood samples from both the Pietrains (P less than 0.001) and the crossbreds (P less than 0.05). Of the swine which were tested for erythrocyte selenium-dependent glutathione peroxidase activity, values were within acceptable laboratory limits in 18 of 20 Pietrains, 14 of 14 halothane test-negative crossbreds, and 8 of 8 halothane test-positive crossbreds. In 2 of 20 Pietrains, a 35% deficiency of this enzyme was found. Heinz bodies were not detected in erythrocytes examined from 21 Pietrains, 20 crossbred swine (8 halothane test positives), and 12 controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Porcine malignant hyperthermia susceptibility: erythrocytic osmotic fragility. 402 25

In an attempt to develop a diagnostic test for malignant hyperpyrexia (MH) without the need for open muscle biopsy, we have investigated the change in heat production brought about when platelets and muscle are exposed to halothane and caffeine. Halothane 3% caused platelet aggregation, which was itself associated with heat production. Caffeine 4 mmol litre-1 decreased heat production in platelets from both MH susceptible and non-susceptible individuals. Muscle exposed to 4% halothane showed an increase in heat production in both types of tissue. There were no significant differences in heat production between MH-susceptible and non-susceptible tissue in any of the tests.
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PMID:Microcalorimetric studies in malignant hyperpyrexia susceptible individuals. 404 26

Halothane itself (1--3 vol percent) produced no significant changes in either Td or dT/dt max of the isolated hemidiaphragm during direct electrical stimulation. On the other hand, halothane significantly potentiated the effect of aminophylline on the resting tension of the muscle, both in a resting non-stimulated muscle and during direct electrical stimulation. Diethyl-ether did not affect the action of aminophylline on the resting tension. The interaction between halothane and aminophylline can be taken as a model for malignant hyperpyrexia. Procaine regularly produced further potentiation of the halothane-aminophylline interaction. There was no halothane-aminophylline interaction in a calcium-free medium. Verapamil was found to potentiate the halothane-aminophylline interaction, whereas di-Na-EDTA depressed it. Halothane did not significantly affect the actions of isoprenaline and adrenaline on Td and dT/dt max during direct electrical stimulation. So far, there is no obvious molecular basis for the action of halothane, but the available evidence indicates that its action is taking place both on the cell membrane and inside the cell, probably by blocking the reaccumulation of calcium in the sarcoplasmic reticulum and thus increasing the amount of free calcium in the cell.
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PMID:Interaction of halothane and aminophylline on the isolated hemidiaphragm of the rat. 676 97

Since the cellular defect of malignant hyperthermia (MH) may occur in tissues other than muscle and since platelets share certain contractile characteristics with muscle cells, testing platelets has been suggested as a way to diagnose susceptibility to MH. In analogy to the in vitro depletion of muscle adenosine triphosphate (ATP), the authors compared platelet basal nucleotide levels and halothane-induced depletion of ATP from 10 MH-susceptible patients and from 12 unrelated nonsusceptible controls. A rapid and simple isocratic high-pressure liquid chromatography technique was used to analyze acid-extracted platelet nucleotides. Halothane added to platelet-rich plasma at 37 degrees C significantly decreased ATP in platelets in a dose-dependent as well as a time-dependent manner. In contrast, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were not changed significantly. Other volatile anesthetic agents also depleted ATP in platelets. Although ATP in platelets exposed to halothane was depleted significantly, there was no difference between platelets from MH-susceptible patients and nonsusceptible controls. Therefore, halothane-induced ATP depletion in platelets is not a reliable test for diagnosing MH susceptibility.
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PMID:Halothane-induced ATP depletion in platelets from patients susceptible to malignant hyperthermia and from controls. 683 75

Malignant hyperthermia (MH) was observed in three cases of Halothane anesthesia performed in six littermate pigs. In two pigs, MH was totally reversed by the intravenous administration of Dantrolene 2 or 3 mg/kg. In one pig, an injection of 2 mg/kg reversed the MH symptoms transiently Dantrolene had no effect on the serum lactate values elevated in the MH-positive pigs. The therapeutic use of Dantrolene appears to be indicated in the stress-susceptible pigs.
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PMID:Halothane induced porcine malignant hyperthermia reversed by dantrolene. 688 29

Malignant hyperthemia, which can be initiated in susceptible humans and swine by the volatile anesthetic halothane, appears to result from abnormal responses in skeletal muscle. We have inferred the primary defect in susceptible muscles by observing their responses to certain drugs. Furthermore, we compared the responses of cut muscle cell preparations, such as those used in the diagnostic caffeine test, with those of intact muscle cells. Specifically, we investigated the effects of halothane, caffeine, succinylcholine and catecholamines on the mechanical properties of intact muscle cells from normal pigs, mice and frogs and susceptible pigs. The results from intact and paired cut cell preparations were qualitatively similar. Halothane (2%) caused a 30% decrease in peak tetanic tension in susceptible porcine muscle but less than a 10% change in other muscles. Halothane potentiated twitch tension in frog and susceptible pig muscle. The latter was 4 times more sensitive to caffeine twitch potentiation than normal muscle. Porcine intercostal muscles were more sensitive to caffeine than limb extensor muscles and the difference between normal and susceptible muscle was less with intercostal muscles. Succinylcholine and catecholamines had small and opposite effects on porcine muscles; when used together in combination with halothane there was little effect on normal muscle but a dramatic decrease in tetanic tension and rapid onset of contracture in susceptible muscle.
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PMID:Mechanical properties of normal and malignant hyperthemia susceptible porcine muscle: effects of halothane and other drugs. 696 21

We have compared and contrasted two diagnostic tests for Malignant Hyperthermia (MH) - the Caffeine-Halothane Contracture Test and the Caffeine Skinned Fibre Tension Test. Both tests show a strongly positive relationship both with the occurrence of MH reactions and with each other. The former test is more rapid and requires less skill. The latter test can be performed on much less muscle and permits storage of the muscle over prolonged periods of time.
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PMID:Comparison of the caffeine skinned fibre tension (CSFT) test with the caffeine-halothane contracture (CHC) test in the diagnosis of malignant hyperthermia. 713 94


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