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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the absence of halothane challenge, incubates of skeletal whole-muscle homogenates from malignant-hyperthermia-susceptible humans and pigs exhibit greater free fatty acid production than controls, which has been attributed to elevated phospholipase A2 activity. The present study examines lipid profiles of human muscle (vastus lateralis) prior to halothane challenge, relating the lipid profiles to the magnitude of halothane contracture response in muscle from the same biopsy. No differences in cholesterol, phospholipids or free fatty acids were observed among preparations exhibiting low, moderate or strong responses to halothane. Two fatty acids associated with triglycerides (palmitoleic and oleic) were significantly (P less than 0.05) lower in muscle demonstrating a strong response to halothane. These results do not support altered phospholipase A2 activity as a defect in malignant hyperthermia, but rather support an enhanced turnover of triglycerides in biopsied skeletal muscle from MH-susceptible humans.
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PMID:Triglycerides, not phospholipids, are the source of elevated free fatty acids in muscle from patients susceptible to malignant hyperthermia. 279 95

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.
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PMID:Effects of anaesthetic agents on erythrocyte fragility: comparison of normal and malignant hyperthermia susceptible patients. 360 52

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.
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PMID:Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2. 366 Apr 10

Malignant hyperthermia (MH), a genetically inherited disorder of skeletal muscle, is due to molecular defect in membrane permeability. The alteration in membrane permeability is suggested to be due to enhanced phospholipase A2 activity which is responsible for the increased level in sarcoplasmic Ca2+. The excess Ca2+ is responsible for muscle hyper-rigidity and enhanced rate of glycolysis, resulting in a rapid rate of lactic acid production and a low pH in MH muscle.
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PMID:Malignant hyperthermia: molecular defects in membrane permeability. 388 61

The interaction of Ca2+ with mitochondria isolated from longissismus dorsi, a predominantly white skeletal muscle, of normal and malignant hyperthermia pigs was investigated using tightly-coupled preparations. Arrhenius plots of mitochondrial Ca2+ -stimulated respiration for succinate oxidation of malignant hyperthermia pigs showed a transition temperature (Tt) of 26.31 +/- 0.80 degrees C (n = 5), which was decreased by spermine to 15.41 +/- 0.69 degrees C (n = 3), a value very similar to that for normal pigs. No difference in either the Tt or in the activation energy (Ea) was observed between the two types of pigs when ADP was used instead of Ca2+. Mitochondria of malignant hyperthermia pigs were uncoupled at 40 degrees C by exogenous Ca2+ at 1221 +/- 301 (n = 9) nmol Ca2+ per mg proteinn during succinate oxidation and the uncoupled mitochondria showed large amplitude swelling. Both the Ca2+ -induced uncoupling and swelling were prevented by bovine serum albumin and by the phospholipase inhibitors, spermine and tetracaine. In contrast, mitochondria of normal pigs were still tightly coupled even after a total addition of 2313 +/- 287 (n = 5) nmol Ca2+ per mg protein and retained the original condensed configuration in the presence or absence of spermine and tetracaine. Mitochondria of malignant hyperthermia pigs contained significantly (P less than 0.001) higher quantities of endogenous Ca2+ and showed a significantly (P less than 0.001) faster FCCP-induced endogenous Ca2+ efflux rate than normal when monitored spectroscopically with murexide. No significant difference was observed in either the rate of exogenous Ca2+ uptake or in the extent of Ca2+ accumulated in the aerobic steady state during succinate oxidation between the two types of pigs. The rate of mitochondrial Ca2+ efflux of malignant hyperthermia pigs during anaerobiosis was about twice that of normal. Experimental evidence suggests that mitochondria from musculi longissimus dorsi of malignant hyperthermia pigs contained a Ca2+ -stimulated phospholipase A2 (EC 3.1.1.4, phosphatide 2-acylhydrolase), and that this enzyme if present in mitochondria of normal pigs is either latent or in very low concentration. The significance of the Ca2+ -stimulated phospholipase A2 and its association with the enhanced rate of glycolysis in porcine malignant hyperthermia syndrome and in the post-mortem formation of the pale, soft and exudative conditions observed in white skeletal muscles of malignant hyperthermia pigs is discussed.
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PMID:Mitochondrial calcium transport and calcium-activated phospholipase in porcine malignant hyperthermia. 747 May