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 purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors.
Anesthesiology 1991 Sep
PMID:Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. 171 78

A few cases of non-anaesthetic-induced rhabdomyolysis in humans, predisposed to malignant hyperthermia (MH), have been described in literature. We studied a group of 6 consecutive patients with unexplained and recurrent attacks of rhabdomyolysis with the test used to determine susceptibility to MH, the in vitro contraction test (IVCT). The results of the IVCT showed 5 of these 6 patients to be MH susceptible. In cultured muscle cells from one of these patients a disturbed calcium homeostasis could be demonstrated. The relation between MH and recurrent rhabdomyolysis is discussed.
J Neurol Sci 1991 Sep
PMID:In vitro contraction test for malignant hyperthermia in patients with unexplained recurrent rhabdomyolysis. 179 72

Hyperthermia from septic shock may be indistinguishable from malignant hyperthermia. Dantrolene may be given in septicemia if the diagnosis is unclear. To determine if dantrolene is safe to use in sepsis, two studies were performed. In study 1, 18 anesthetized dogs in which profound septic shock was induced with 5 mg/kg of intravenous Escherichia coli endotoxin were randomized to receive (30 min later) intravenous injections of 10 mg/kg of dantrolene solution, the diluent of dantrolene, or maintenance intravenous fluids alone. The use of dantrolene solution and the diluent of dantrolene resulted in similar but transient statistically significant increases in the cardiac filling pressures and cardiac outputs and decreases in the vascular resistances compared with the control dogs. In a second study, 185 rats were randomized into five equal groups. Groups 1, 2, and 3 received 15 mg/kg of intraperitoneal Escherichia coli endotoxin followed 30 min later by 10 mg/kg of dantrolene solution, the diluent of dantrolene, or normal saline. Groups 4 and 5 received normal saline followed by dantrolene or normal saline. The survival of groups 1, 2, and 3 was less at 24 h (P less than 0.0001) than that of either control group, but was not significantly different from one another. The results suggest dantrolene can be administered safely under clinical conditions where the cause of hyperthermia and shock cannot clearly be ascribed to malignant hyperthermia or septicemia.
Anesth Analg 1991 Sep
PMID:Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats. 186 22

The genetics of malignant hyperthermia (MH) are ill-understood; however, the association of Duchenne muscular dystrophy (DMD) with MH is well known. A deficiency of dystrophin is common to both the DMD and mdx mouse, an animal model for DMD. Using muscle contracture tests for MH, we have shown that in the mdx mouse there is no MH susceptibility, suggesting the lack of a direct role of the dystrophin in the development of MH syndrome.
Metabolism 1991 Sep
PMID:Negative halothane-caffeine contracture test in mdx (dystrophin-deficient) mice. 189 52

This report describes a cardiac arrest that occurred in a 4-month-old infant during induction of anesthesia. During the administration of N2O/O2 and halothane via a face mask tachycardia was noted and rigor followed the application of succinylcholine for intubation. Shortly thereafter cardiac arrest occurred; 15 min later we found a profound metabolic acidosis as well as signs of rhabdomyolysis with a serum potassium level of 10.3 mmol/l and an increase in serum creatine kinase (CK). While performing cardiopulmonary resuscitation (CPR) and treating the acid-base imbalance and hyperkalemia, we administered--suspecting malignant hyperthermia (MH)--dantrolene. Approximately 60 min post-arrest we achieved stabilization of the vital signs. During the following hours the CK level rose to 99, 600 IU/l and myoglobinuria of 360,000 micrograms/l confirmed the extent of the rhabdomyolysis. The infant was discharged home without detectable sequelae after 2 1/2 weeks. Comparisons with corresponding case reports in the literature lead to the supposition that our patient suffered from a myopathy thus far undiagnosed. To what extent a MH episode may have contributed to the clinical picture cannot be determined at present. The spectrum of adverse reactions to volatile anesthetics and succinylcholine in patients with myopathic disorders is presented and discussed. As in other case reports, the dramatic course described here also demonstrates that in addition to CPR and treatment of the acid-base and electrolyte imbalances, administration of dantrolene should be considered at an early stage.
Anaesthesist 1991 Sep
PMID:[Cardiac arrest during anesthesia induction with halothane and succinylcholine in an infant. Massive hyperkalemia and rhabdomyolysis in suspected myopathy and/or malignant hyperthermia]. 195 45

The role of succinylcholine in the precipitation of malignant hyperthermia (MH) necessitates the testing of new neuromuscular relaxants for their ability to trigger MH in MH-susceptible swine before general human use. We tested doxacurium and mivacurium, two new nondepolarizing bis-benzylisoquinolinium neuromuscular relaxants, at ED95 and at four times ED95 doses in swine previously documented to be MH-susceptible. In none of the 16 animals was MH triggered after administration of these relaxants, whereas all animals developed fatal MH after administration of halothane or halothane plus succinylcholine. Muscle biopsy specimens taken before administration of the relaxant confirmed that all animals had increased sensitivity to halothane, caffeine, or both. Thus, we conclude that doxacurium and mivacurium are not triggering agents of malignant hyperthermia in MH-susceptible swine.
Anesth Analg 1990 Sep
PMID:Doxacurium and mivacurium do not trigger malignant hyperthermia in susceptible swine. 214

The region of intron A of the rat renin gene containing a unique tandemly repeated sequence was analysed in the Milan and Lyon hypertensive rat strains and their controls, and in several Sprague-Dawley rats, using an oligonucleotide probe complementary to the tandemly repeated sequence and a renin complementary DNA probe. In the Milan rats, the size of the Bgl II DNA fragment encompassing the tandem repeat region was the same in the hypertensive (MHS) and normotensive (MNS) strains. In the Lyon model, a difference of 1.1 kilobase (equivalent to about 28 copies of the 38 basepair tandem repeat sequence) was observed in the size of the Bgl II fragment of the hypertensive (LH) and normotensive (LN) strains. However, the finding that the size of the fragment in the Lyon low-blood-pressure (LL) strain was the same as that in the LH strain rather than the LN strain suggests that the difference between the two latter strains is not by itself a major cause of the blood pressure difference between them in the intron A tandem region. An analysis of Sprague-Dawley rats, from which the Lyon strains are derived, showed that at least three different renin gene alleles, two with Bgl II fragments of the same size as those seen in the Lyon strains, are randomly segregating in this population.
J Hypertens 1990 Sep
PMID:Analysis of the renin gene intron A tandem repeat region of Milan and Lyon hypertensive rat strains. 217 69

Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine.
Can J Anaesth 1990 Sep
PMID:The importance of calcium ions for in vitro malignant hyperthermia testing. 220 45

Muscle relaxation rate following a tetanic stimulus of adductor pollicis muscle was measured prospectively in 26 patients potentially susceptible to malignant hyperthermia (MH) the day before a muscle biopsy was obtained for MH in vitro screening. Eleven subjects were found to be MH susceptible (MHS) and 15 subjects MH-negative (MHN). In all patients, relaxation rate was recorded at three different temperatures of the skin overlying adductor pollicis (30, 34 and 38 degrees C) achieved by a small surface heating unit placed over the thenar eminence. The MHS group exhibited slightly higher relaxation rate at 34 and 38 degrees C compared with the MHN group and this difference was accentuated with increasing temperature, but was not statistically different. The results of the present study suggest that relaxation rates are normal in MHS individuals under physiological conditions and cannot be used diagnostically for MH screening.
Br J Anaesth 1990 Sep
PMID:Muscle relaxation rates in individuals susceptible to malignant hyperthermia. 222 71

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.
Kidney Int 1990 Sep
PMID:Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. 223 87


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