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)

The adenosine triphosphate (ATP depletion ratio, which is the ratio [ATP] in skeletal muscle equilibrated with carbogen and 4% halothane for 30 minutes divided by [ATP] in skeletal muscle equilibrated with carbogen alone for 30 minutes is less than normal in most but not in all rigid MHS patients. The ratio is normal in non-rigid MHS patients. This diagnostic tool is, therefore, useful in the diagnosis of rigid MH. It is not, however, such a sensitive diagnostic parameter as the caffeine contracture test.
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PMID:The adenosine triphosphate (ATP) depletion test: comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility. 99 Sep 79

Skeletal muscle from malignant hyperthermic (MH) pigs incubated at 37 C in 2.3 mM calcium-Krebs-Ringer solution contracts spontaneously when exposed to halothane. In contrast, halothane did not induce contracture in MH muscle incubated in 2.3 mM calcium-Krebs-Ringer solution at 25 C or in calcium-free Krebs-Ringer's solution at 37 C. Halothane did not induce contracture in normal control muscle in 2.3 mM Krebs-Ringer solution at 25 or 37 C. In the presence of halothane, addition of caffeine produced greater contracture in MH muscle than in normal controls. Halothane-caffeine-induced contractures of MH and control muscles at 25 and 37 C were similar. Elucidation that under certain experimental conditions halothane induces contracture in MH muscle, but not in normal muscle 1) may aid in development of a diagnostic test; 2) establishes further evidence for skeletal muscle as the target tissue for anesthetic-induced MH; 3) suggests that halothane may affect systems that regulate sarcoplasmic calcium concentration below contracture threshold in MH muscle. (Key words: Hyperthermia, malignant; Anesthetics, volatile, halothane; Ions, calcium; Muscle, skeletal, malignant hyperthermia.).
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PMID:Porcine malignant hyperthermia: effects of temperature and extracellular calcium concentration on halothane-induced contracture of susceptible skeletal muscle. 111 84

Isoflurane has a lesser ability than halothane to induce contracture in malignant hyperthermia (MH) muscle in vitro. This does not necessarily imply that isoflurane is not as potent an MH trigger as halothane in vivo. A hypothesis was tested that in vitro treatment with Bay K 8644, an activator of both the dihydropyridine receptors as well as the sodium channels of the T-tubules, potentiates isoflurane-induced MH-susceptible skeletal muscle contracture. In addition to the usual halothane-caffeine test, other muscle bundles were exposed to 10 microM Bay K 8644-halothane and equipotent anesthetic concentrations (expressed in multiple minimum alveolar concentration [MAC]) of isoflurane either alone or combined with Bay K 8644. In 14 MH-susceptible muscle bundles, the mean maximum contracture induced by 2 MAC isoflurane was 0.20 +/- 0.22 g (mean +/- SD), and this value was significantly less than that obtained with 2 MAC halothane (0.68 +/- 0.40 g). Bay K 8644 did not induce muscle contracture on its own but consistently enhanced both the 0.5 MAC isoflurane and halothane to the same maximal isometric tension (1.09 +/- 0.35 g and 1.11 +/- 0.37 g, respectively). Such an effect was not observed in the MH-nonsusceptible group. Under the conditions of this in vitro study, 0.5 MAC isoflurane appears to be as potent as halothane in inducing muscle contracture in skeletal muscle bundles from individuals susceptible to MH.
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PMID:Effect of Bay K 8644 on the magnitude of isoflurane and halothane contracture of skeletal muscle from patients susceptible to malignant hyperthermia. 137 90

Two patients in a family of exertion-induced heat stroke were reported. Case 1: A 23-year-old male, paternal cousin of case 2, was admitted to our hospital because of loss of consciousness during running under a burning sun. On physical and neurological examinations, he was deeply comatose with high fever, tachycardia, and increased deep tendon reflexes. Laboratory findings disclosed rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, liver injury, and brain edema. He recovered after intensive cooling, some antibiotics, glycerol and sodium dantrolene administration. Case 2: A 19-year-old male experienced loss of consciousness and high fever during playing soccer at 15 years of age, and was admitted to a hospital. On admission, he had high fever of 38.7 degrees C, and increased serum CK level. He recovered two weeks after admission. He was readmitted to our hospital to evaluate the predisposition for malignant hyperthermia. His physical and neurological examinations showed no abnormalities. Routine laboratory findings were within normal limits. Muscle biopsy findings of cases 1 and 2 were mildly increased number of fibers with centrally placed nuclei. Caffeine test on skinned muscle fibers from the biopsies showed normal response in both type 1 and 2 fibers. The present patients were diagnosed as having exertion-induced heat stroke, but with no increased muscle fiber sensitivity to caffeine, suggesting that the pathomechanism differs from that of malignant hyperthermia induced by malfunction of sarcoplasmic reticulum.
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PMID:[Two familial cases with exertion-induced heat stroke--relationship to malignant hyperthermia]. 139 27

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed in 96 patients according to the protocol of the European MH Group. In addition, tests were performed with halothane 0.44 mmol l-1 and 0.66 mmol l-1, and caffeine 2 mmol l-1, each added as a single bolus dose to fresh specimens. For all tests the size of contractures were recorded, and for the diagnostic tests the halothane and caffeine threshold concentrations were determined (i.e. the minimal concentrations eliciting a contracture of 0.2 g). The caffeine specific concentration (CSC, i.e. the concentration increasing force 1.0 g) and the % increase with caffeine 2 mmol l-1 were calculated from the dose response curves. Various diagnostic criteria in use by the North American MH Group were applied, and diagnostic outcome compared with the result obtained by the protocol of the European MH Group. Thirty-five patients were susceptible to MH (MHS), 33 were non-susceptible (MHN), and 28 had equivocal results of the tests (MHE). Additional tests were made in 34 MHS, 32 MHN, and 26 MHE patients. Contractures elicited by bolus addition of halothane or caffeine were significantly larger than those observed following the same dose of drug added cumulatively (P less than 0.05). Contractures greater than or equal to 0.7 g following halothane 3% (bolus dose) were seen in 78% of MHS patients and 18% of MHN patients, A CSC less than 4 mmol l-1 was elicited in 86% of MHS and 30% of MHN patients, whereas an increase in force greater than or equal to 4% or greater than or equal to 7% was seen in 71% and 34% of MHS patients, respectively, and in none of the MHN patients. Using the criterion of greater than or equal to 0.7 g in the halothane test and greater than or equal to 4% increase in the caffeine test gave the best agreement between diagnostic outcome with the European and North American protocols: All 34 MHS patients (100%) were positive to one or more tests, but so were eight of 32 MHN patients (25%), giving an overall diagnostic agreement of 88%. We conclude that, in our laboratory, the results obtained with the two major protocols for investigation of MH susceptibility are not identical. Patients surviving fulminant MH, however, react abnormally to nearly all the tests. For validation and possibly further standardization of the tests each laboratory must investigate a large number of normal controls and as many patients surviving fulminant MH as possible.
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PMID:Sources of variability in halothane and caffeine contracture tests for susceptibility to malignant hyperthermia. 139 23

We investigated Greyhounds because of prior reports of malignant hyperthermia (MH) episodes and because Greyhounds may express high genetic relatedness due to inbreeding for generations. Seven Greyhound and six mongrel dogs were given halothane and succinylcholine anesthesia as a challenge to trigger MH. They also underwent semitendinosus muscle biopsy for contracture study with halothane and caffeine. Measurements in vivo of mixed venous and arterial blood gases, cardiac output by thermodilution, temperature, blood pressure, and pulse rate provided sequential data regarding whole body O2 consumption (product of cardiac output and arterial-mixed venous O2 content difference), acid-base status, and arterial CO2 tension. Greyhounds and mongrels had uniformly similar in vivo and in vitro responses, without evidence for MH. Contracture thresholds were higher than those reported for normal swine and humans (8 mM vs. 4 mM). Information on MH susceptibility in this breed is important for laboratory investigation in Greyhounds as well as to veterinary medicine in general. Neither mongrels nor this group of Greyhounds were obviously susceptible to MH. If all Greyhounds are genetically homologous, then Greyhounds may not be specifically MH susceptible. These findings overall may provide a protocol and baseline normal comparative data for determining MH susceptibility in dogs and other species.
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PMID:Evaluation of greyhound susceptibility to malignant hyperthermia using halothane-succinylcholine anesthesia and caffeine-halothane muscle contractures. 146 Aug 48

The "K-type" designation is used to describe a patient being investigated for malignant hyperthermia (MH) when concurrent administration of caffeine and halothane induces muscle contracture (rigidity, spasm) in vitro, but when halothane and caffeine given separately produce a normal response. It is accepted in some centres that K-type individuals are susceptible to malignant hyperthermia (MHS). In this paper, the K-type is shown not to correlate with the MH susceptible (MHS) status as accepted by the European MH group.
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PMID:Is the "K-type" caffeine-halothane responder susceptible to malignant hyperthermia? 831 43

1. Malignant hyperpyrexia (MH) is an inherited muscle abnormality that presents clinically as a syndrome of life-threatening complications during general anaesthesia. 2. Propofol is a new sedative hypnotic used for the induction and maintenance of anaesthesia. 3. Propofol did not induce MH in five susceptible pigs. Propofol did not induce contracture in isolated MH susceptible muscle but did modify halothane, caffeine and KCl contractures.
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PMID:Propofol anaesthesia in malignant hyperpyrexia susceptible swine. 152 53

A defect in the skeletal muscle sarcoplasmic reticulum (SR) calcium release channel of malignant hyperthermia-susceptible (MHS) pigs greatly enhances SR calcium release in pigs homozygous for the malignant hyperthermia (MH) gene. In pigs heterozygous at this locus, rates of calcium release from isolated SR stimulated by Ca2+, ATP, or caffeine are intermediate to those of both MHS and normal SR [Mickelson et al. Am. J. Physiol. 257 (Cell Physiol. 26): C787-C794, 1989]. In this study bundles of intact muscle cells dissected from pigs of various genotypes were used to examine the effects of the MH gene on contractile responses to caffeine (direct stimulation of the SR) or to surface membrane (sarcolemma) depolarization (i.e., stimulation by way of the steps in excitation-contraction coupling). The caffeine threshold for contractures in the heterozygous muscles (5 mM) was intermediate to both types of homozygous muscles (2 mM for MHS and 10 mM for normal) as is the case with direct stimulation of calcium release from SR vesicles [Mickelson et al. Am. J. Physiol. 257 (Cell Physiol. 26): C787-C794, 1989]. Sarcolemmal depolarization was elicited by electrical stimuli or elevated extracellular potassium. Control twitch tension for MHS and heterozygous muscles did not differ and was significantly greater in both than in homozygous normal muscles. Potassium-induced contractures were significantly larger in MHS and heterozygous than in normal muscles. Thus, in heterozygous muscles, force production via sarcolemmal depolarization (twitches and potassium contractures) was enhanced as much as in homozygous MHS muscles. This could be the result of feedback from abnormal SR calcium channels producing altered (enhanced) transverse tubule to SR signal transduction.
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PMID:Excitation-contraction coupling in pigs heterozygous for malignant hyperthermia. 153 30

Malignant hyperthermia (MH) is a rare genetic myopathy that was first described as a fatal complication of general anesthesia in 1960. It is estimated to affect approximately 1 in 15,000 pediatric patients and 1 in 40,000 adult middle-aged patients. The mode of transmission is genetic: the severest form is autosomal dominant, and the less severe, autosomal recessive. Thus, both men and women can have MH, although there is a slightly higher incidence in the male pediatric population. Malignant hyperthermia is usually triggered by halogenated anesthetic agents with or without depolarizing muscle relaxants. The classic diagnostic triad consists of skeletal muscle rigidity, metabolic acidosis, and elevated body temperature. The definitive diagnosis is suspected susceptible individuals is revealed by exposing an intact muscle fiber to caffeine and halothane in varying concentrations. An abnormal contracture response is hypothesized to be the result of an increase in the release of calcium ion from the sarcoplasmic reticulum in response to neuronal stimulation leading to a hypermetabolic state. The mainstay of treatment is dantrolene, given either prophylactically in susceptible patients or immediately whenever a malignant hyperthermic episode is suspected.
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PMID:Malignant hyperthermia: a review. 156 Feb 93


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