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)

This is the first report of a case of malignant hyperthermia (MH) from Saudi Arabia. MH was probably triggered by response to Halothane. The diagnosis was suspected by the clinical signs of tachycardia, severe rigidity, cyanosis and rising temperature. The case was successfully managed by vigorous cooling, dantrolene sodium and diuresis.
 ...
PMID:Malignant hyperthermia in a Saudi child. 299 70

Sarcolemmal properties implicated in the skeletal muscle disorder, malignant hyperthermia (MH), were examined using sarcolemma-membrane vesicles isolated from normal and MH-susceptible (MHS) porcine skeletal muscle. MHS and normal sarcolemma did not differ in the distribution of the major proteins, cholesterol or phospholipid content, vesicle size and sidedness, (Na+ + K+)-ATPase activity, ouabain binding, or adenylate cyclase activity (total and isoproterenol sensitivity). The regulation of the initial rates of MHS and normal sarcolemmal ATP-dependent calcium transport (calcium uptake after 1 min) by Ca2+ (K1/2 = 0.64-0.81 microM), calmodulin, and cAMP-dependent protein kinase were similar. However, when sarcolemmal calcium content was measured at either 2 or 20 min after the initiation of active calcium transport, a significant difference between MHS and normal sarcolemmal calcium uptake became apparent, with MHS sarcolemma accumulating approximately 25% less calcium than normal sarcolemma. Calcium transport by MHS and normal sarcolemma, at 2 or 20 min, had a similar calmodulin dependence (C1/2 = 150 nM), and was stimulated to a similar extent by cAMP-dependent protein kinase or calmodulin. Halothane inhibited MHS and normal sarcolemmal active calcium uptake in a similar fashion (half-maximal inhibition at 10 mM halothane), while dantrolene (30 microM) and nitrendipine (1 microM) had little effect on either MHS or normal sarcolemmal calcium transport. After 20 min of ATP-supported calcium uptake, 2 mM EGTA plus 10 microM sodium orthovanadate were added to initiate sarcolemmal calcium efflux. Following an initial rapid phase of calcium release, an extended slow phase of calcium efflux (k = 0.012 min-1) was similar for both MHS and normal sarcolemma vesicles. We conclude that although a number of sarcolemmal properties, including passive calcium permeability, are normal in MH, a small but significant defect in MHS sarcolemmal ATP-dependent calcium transport may contribute to the abnormal calcium homeostasis and altered contractile properties of MHS skeletal muscle.
 ...
PMID:Skeletal muscle sarcolemma in malignant hyperthermia: evidence for a defect in calcium regulation. 302 85

Malignant hyperthermia is a potentially lethal syndrome that can be triggered by inhaled anesthetics. Thus, it may be appropriate to utilize equipment that minimizes exposure of susceptible patients to inhaled anesthetics. The rate of release of anesthetic stored in anesthesia delivery systems is unknown. To determine residual anesthetic concentrations, the washout rates of halothane and isoflurane were compared, and the effects of a 1-l/min and a 10-l/min fresh gas flow were evaluated. Halothane concentrations were also measured in samples taken from the fresh gas outlet and the Y-piece of the circle system during four separate studies in which various components of the anesthesia system were replaced. In each study an Ohio Modulus anesthesia machine equipped with an Air-Shields ventilator was exposed to 2% halothane for 18 h. Anesthetic concentrations were determined by a gas chromatograph having a sensitivity of 0.1 ppm. Isoflurane washed out 3-4 times faster than halothane. Residual halothane concentration was approximately equal to tenfold greater when the fresh gas flow was 1 l/min rather than 10 l/min: 194 versus 19 ppm after 1 h of washout. Using a 10-l/min fresh gas flow, halothane concentrations in samples obtained from the Y-piece were similar with original or fresh soda lime but were more than tenfold lower after the fresh gas outlet hose and circle system were replaced (approximately equal to 50 ppm vs. approximately equal to 5 ppm after 5 min of washout).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Preparation of anesthesia machines for patients susceptible to malignant hyperthermia. 316 44

Animals were identified as porcine malignant hyperthermia susceptible by halothane testing and were slaughtered at 90 kg of body weight. Coronary, renal and iliac arteries were isolated, dissected and 5 mm rings were mounted in 20 mL organ baths with modified Krebs solution maintained at 37 degrees C and oxygenated with 95% O2, 5% CO2. Halothane at 0%, 0.5%, 2% and 5% concentration was bubbled in the organ baths and mechanical responses were recorded over a period of 25 min. Halothane free arteries remained quiescent and the arteries from the halothane sensitive and from the halothane resistant groups reacted similarly. All arteries in the presence of halothane responded with an initial contraction of short duration followed by a relaxation and both phenomena occurred in a concentration-dependent fashion. The iliac artery was the most sensitive to halothane and responded to 0.5% concentration while coronary and renal arteries maintained the resting tension of 4 g. These results demonstrate that vascular smooth muscle, like skeletal muscle and unlike respiratory smooth muscle, has a direct pharmacological response to halothane. These observations led to the postulate that halothane by its transient but significant vasoconstrictive action could be a contributing factor to initiate the fulminant reactions occurring in malignant hyperthermia.
 ...
PMID:Halothane induced vasomotion of coronary, renal and iliac arterial rings in malignant hyperthermia susceptible swine. 319 69

We report a family in which two sisters with myotonia congenita (MyC) were referred for malignant hyperthermia (MH) evaluation after each developed muscle rigidity with anesthesia. Halothane contracture testing of skeletal muscle in both was consistent with MH susceptibility. A third sister without clinical evidence of MyC was negative on contracture testing. These results suggest an association between MyC and MH susceptibility.
 ...
PMID:Malignant hyperthermia in myotonia congenita. 336 83

Twenty-seven patients, four of whom had presented with a crisis of malignant hyperthermia and the 23 other being close relatives of such patients, underwent a muscle biopsy so as to determine their susceptibility to malignant hyperthermia. Halothane-caffeine contracture tests, interpreted in accordance with the criteria of the European Group on Malignant Hyperthermia, yielded the following results: 13 positive (MHS), 10 negative (MHN), 4 equivocal (MHE). The history, clinical examination, CPK level, histoenzymatic morphology and electron microscopic study did not provide information sensitive enough to use for the detection of susceptibility to malignant hyperthermia. This confirmed the literature: the halothane-caffeine contracture test remains the only reliable diagnostic test to detect this susceptibility, despite the search for non invasive tests. If the mechanism of triggering a contracture to increasing doses of caffeine is well known in normal muscle, it is the smaller concentrations required which suggests malignant hyperthermia abnormality. The halothane effect is less well understood. A concentration less than or equal to 2 vol % yields a contracture only in MHS muscle. Differences in protocols used by American authors emphasize the importance of standardization as used by the European Group, which is the only way of collecting and comparing results on well over a thousand patients. This confrontation should reduce the number of equivocal diagnoses and allow a correct classification of patients at risk or their relatives as MHS or MHN.
 ...
PMID:[Tests of contracture and sensitivity to malignant hyperthermia in 27 patients]. 336 12

Fura-2 was used to estimate myoplasmic [Ca2+] in intact intercostal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs. Small muscle bundles (20-50 fibers) were loaded with the membrane-permeant form of the dye. Resting myoplasmic [Ca2+] were not significantly different in normal and MHS muscles. Halothane produced increases in myoplasmic Ca2+ with associated contractures in MHS muscles, but not in normal muscles. These halothane effects were reversible. Caffeine produced increases in myoplasmic Ca2+ and contractures in both MHS and normal muscles. The threshold concentrations were lower in the MHS muscles. The correlations between myoplasmic [Ca2+] and force in MHS and normal muscles were similar.
 ...
PMID:Fura-2 detected myoplasmic calcium and its correlation with contracture force in skeletal muscle from normal and malignant hyperthermia susceptible pigs. 341 68

The effects on erythrocyte fragility of two general anaesthetic agents (halothane and ethanol) and succinylcholine were examined using preparations from 13 normal and four malignant hyperthermia susceptible patients. Erythrocyte fragility was determined by the degree of haemolysis induced in solutions of decreasing osmolarity of NaCl. Halothane caused haemolysis of erythrocytes in an isoosmolar solution, being more potent at 42 degrees C than at 32 degrees C. Haemolysis produced by an hypoosmolar medium or halothane was potentiated by exogenously added phospholipase A2. Ethanol did not markedly alter the haemolysis of erythrocytes under conditions of decreasing osmolarity. Succinylcholine 10 mM did not significantly alter the susceptibility of erythrocytes to lysis by halothane. No differences in erythrocyte fragility were observed between preparations from normal and malignant hyperthermia susceptible patients under any of the conditions tested, despite the inclusion of malignant hyperthermia triggering agents in some instances. Although sampling a larger patient population might reveal slight differences between the groups, erythrocyte fragility tests do not appear to be useful in differentiating malignant hyperthermia susceptible from normal patients.
 ...
PMID:Effects of anaesthetic agents on erythrocyte fragility: comparison of normal and malignant hyperthermia susceptible patients. 360 52

The fragility of erythrocytes from 21 patients undergoing in vitro skeletal muscle contracture testing for malignant hyperthermia (MH) susceptibility was examined. Osmotic fragility was determined by the degree of hemolysis in buffered saline solutions of decreasing osmotic strength. Halothane-induced fragility was determined in an isotonic solution containing increasing percentages of halothane saturated solution. The effects of six different incubation conditions prior to performing fragility tests were examined in an attempt to optimize discrimination of MH susceptible patients, including the following: 1) no preincubation; 2) 24-hr incubation at 4 degrees C; 3) 72-hr incubation at 4 degrees C; 4) 24-hr incubation at 37 degrees C; 5) 24-hr incubation at 22 degrees C with plasma from an MH-susceptible patient; and 6) 24-hr incubation at 22 degrees C with plasma from a normal patient. Despite examining six different incubating conditions and the two methods of hemolysis induction, no differences in erythrocyte fragility were detected between patients diagnosed as MH susceptible or normal. Erythrocyte fragility testing is not useful for diagnosing MH susceptibility.
 ...
PMID:Erythrocyte fragility screening is not a tool for diagnosis of human malignant hyperthermia. 363 60

Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood cells. Phospholipase A2 (1 microM) alone caused less than 2% hemolysis, despite high levels (54%) of phosphatidylcholine hydrolysis. Incubation of red blood cells with halothane and phospholipase A2 caused 72% hemolysis. Halothane addition caused 100% hydrolysis of all diacylphosphoglycerides by phospholipase A2, suggesting a mutual potentiation. The major products of phospholipase A2 activity, arachidonic acid and lysophosphatidylcholine, when exogenously added, also greatly increased hemolysis induced by halothane, with arachidonic acid most closely resembling the synergism observed with phospholipase A2. Dantrolene (10 microM) and mepacrine (10 microM) significantly antagonized hemolysis induced by halothane and phospholipase A2 or halothane and exogenously added arachidonic acid and lysophosphatidylcholine. Dantrolene and mepacrine did not antagonize phospholipid hydrolysis or free fatty acid levels. Dantrolene and mepacrine antagonized the synergism between halothane and phospholipase A2 most likely by reducing the lytic action of halothane in the presence of arachidonic acid. The red blood cell is a useful model for studying the antagonism of halothane and phospholipase A2 toxicity by dantrolene and mepacrine.
 ...
PMID:Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2. 366 Apr 10


<< Previous 1 2 3 4 5 6 7 Next >>