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

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.
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PMID:Malignant hyperthermia in dogs. 203 26

The case of a 67-year-old patient who suffered an episode of malignant hyperthermia during the extraction of a cataract is described. The outcome was favourable in spite of the lack of sodium dantrolene. Twenty months later the patient was operated on the contralateral eye with local anesthesia presenting no complications. It is worthy of note that the rareness of the syndrome in this age group and in this type of surgery, as well as the probable safeness of local anesthetics in susceptible patients. We also comment on the lack of sodium dantrolene and the nonexistence of a center facilitating information and diagnosis of malignant hyperthermia in our country.
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PMID:[Malignant hyperthermia during cataract extraction in an elderly patient]. 209 Oct 94

This article pertains to malignant hyperthermia (MH). The disease and its physiologic aspects are described, and a general overall view of what takes place at the cellular level during an MH crisis is presented. Also described is the drug of choice, dantrolene sodium, and its functioning during an MH crisis. The care of an MH patient in the PACU is presented, correlating all the above mentioned aspects of MH.
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PMID:Malignant hyperthermia: a potential crisis in the postanesthesia care unit. 238 72

Dantrolene sodium is a drug used in the treatment of spasticity and malignant hyperthermia. It is known to have a myorelaxant effect related to inhibition of the "release" of calcium by the sarcoplasmic reticulum of striated skeletal muscle. A direct cardiac effect which has only recently been suspected was demonstrated in vitro on isolated preparations of sheep Purkinje fibres and ventricular myocardium. Dantrolene caused a spectacular lengthening of the duration of the action potential of Purkinje fibres. This could be due either to an action on the slow calcium current or to stimulation of an ingoing sodium current sensitive to tetrodotoxin (TTX). This effect on the cardiac action potentials could explain the antiarrhythmic properties of dantrolene sodium during attacks of malignant hyperthermia.
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PMID:[In vitro electrophysiological effects of sodium dantrolene on isolated preparations of Purkinje fibers and ventricular myocardium of sheep]. 242 77

Malignant Hyperthermia is a specific potentially fatal condition which occurs in susceptible individuals in response to various triggering mechanisms, of which anesthetic agents have been found to be the most common offenders. Leading symptoms are generalized muscular rigidity and hyperpyrexia. The etiology seems to be associated with some inherited disturbance in muscle metabolism related to calcium regulation. This syndrome is known for 25 years, the mechanism of triggering, the genetics and the treatment have been able to get examined by animal model as malignant hyperthermia syndrome may occur in swine as well. Pharmacological in-vitro studies on biopsy specimen of muscle fragments are presently one of the most accepted means for pre-anesthetic diagnosis, the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis. Neuroleptic Malignant Syndrome which occurs in patients treated with neuroleptics shows almost identical symptoms. Although the pathogenesis is still unknown, most authors believe a neuroleptic-induced alteration of central neuroregulatory mechanisms is involved. Alternative etiologic mechanisms are suggested by the striking similarities noted between the Neuroleptic Malignant Syndrome and Malignant Hyperthermia. Both disorders might be based on common pathophysiologic mechanisms and might be induced in susceptible patients by a variety of pharmacologic agents. The authors present and compare the actual knowledge concerning symptoms, course and therapy of both syndromes on the basis of 126 case studies of the Neuroleptic Malignant Syndrome from literature.
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PMID:[Malignant neuroleptic syndrome and malignant hyperthermia--a comparison]. 242 64

In this article, we present the results we have obtained from experimental and genetic models of human essential hypertension, in order to investigate those findings relevant to understanding the time course and the mechanisms underlying the human disease. With experiments on the renal artery constriction in the conscious dog, we have shown that a kidney lesion can produce a form of hypertension not different, in the established phase, from the essential one and that the onset of this form follows a phasic pattern during which the initial stages are crucial for understanding the mechanisms leading to hypertension. We also consider a rat model (MHS) that spontaneously develops a form of hypertension very similar to the human disease. In this model, we have demonstrated by a kidney cross-transplantation experiment and functional studies that the kidney is responsible for the rise in blood pressure and that the organ dysfunction is probably due to a primary abnormality in ion handling of the cell membrane. This cellular alteration, detected both in MHS erythrocytes and in their kidney proximal tubular cells, should be the cause for the higher rate of kidney Na+ reabsorption observed in the MHS. Comparing this animal model with, at least, a subgroup of humans prone to develop hypertension or already hypertensive, it is possible to detect a series of similarities in the kidney function, hormonal pattern, and cellular function of the two species that allows us to argue that the MHS is a suitable model from which to draw conclusions relevant to the pathogenesis of essential hypertension in some humans.
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PMID:Genetic and experimental hypertension in the animal model-similarities and dissimilarities to the development of human hypertension. 242 88

Transverse tubule (TT) membrane vesicles have been isolated from the skeletal muscle of normal and malignant hyperthermia-susceptible (MHS) pigs. MHS and normal TT did not differ in the distribution of the major proteins, cholesterol, or phospholipid content, (Na+ + K+)-ATPase activity, [3H]ouabain binding, Ca2+-ATPase activity, Mg2+-ATPase activity, or [3H]saxitoxin binding. Furthermore, in the presence of micromolar Ca2+, MHS and normal TT did not differ significantly in the KD values for either [3H]nitrendipine binding (2.7 +/- 0.6 and 3.3 +/- 0.5 nM, respectively) or (-)-[3H]desmethoxyverapamil ([3H]D888) binding (7.2 +/- 0.9 and 6.4 +/- 0.6 nM, respectively). However, in contrast to normal TT, MHS TT exhibited a significantly decreased Bmax for both [3H]nitrendipine binding (26.4 +/- 5.4 for MHS versus 40.6 +/- 3.7 pmol/mg protein for normal TT) and [3H]D888 binding (17.8 +/- 7.0 for MHS versus 37.4 +/- 5.9 pmol/mg protein for normal TT). At calcium concentrations greater than 0.1 mM, there was a greater inhibition of [3H]nitrendipine binding to normal than to MHS TT such that binding was now similar for both preparations. As with purified TT, [3H]nitrendipine binding to MHS muscle homogenates was significantly less than to normal muscle homogenates (109 +/- 20 versus 211 +/- 19 fmol/mg protein, for MHS and normal TT, respectively); this difference was not apparent when 100 mM CaCl2 was included in the binding medium. We conclude that the altered MHS TT dihydropyridine receptor properties may reflect an adaptation of the TT voltage sensing mechanism to the abnormal sarcoplasmic reticulum calcium release channel regulation in MHS muscle.
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PMID:Altered transverse tubule dihydropyridine receptor binding in malignant hyperthermia. 253 21

Mammalian cells have the same hydroelectrolytic composition (high K, low Na), highly different from that of their surrounding. Constancy of cellular composition is insured by the balance between ionic leaks and (Na, K)-pump activity. Ionic leaks, specially sodium, are fundamental. They allow cells to perform a majority of their general and special functions (import of aminoacids, glucose, phosphates; export of acids; nerve influx; muscular contraction; glandular secretion; intestinal and renal reabsorption and secretion). (Na, K)-pump is essential to life. It is a kind of general motor that creates and maintains ionic concentrations differences whose potential energy is dissipated by leaks to perform cellular functions. Constancy of hydroelectrolytic intracellular composition hides that leak and pump rates, equivalent between them, are extremely variable among cell types (more than 200 times), and can increase 4 times in less than one minute within a cell type with cellular activity. In a cell, (Na, K)-pump rate is far from maximum velocity. This rate is adjusted nearly instantaneously to balance variations in leak rates; it may undergo short term modulation by endo or exocellular factors; it may undergo long term changes through synthesis of new enzyme molecules. Studies on whole cells of the balance between leaks and pump rates is necessary to understand these cells physiology and pathology. Balance between leaks and (Na, K)-pump activity is altered in renal cells from hypertensive rats, spontaneously (SHR) or genetically selected (Milan Hypertensive Strain: MHS). Strikingly, sodium activation of (Na, K)-pump of inner medullary collecting duct cells of MHS rats is greatly blunted compared to controls.
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PMID:[Physiologic role of the sodium pump. Implications for the study of arterial hypertension]. 255 38

Voltage-activated ion currents were measured in cultured skeletal muscle myoballs. Cultures were generated from biopsies from patients referred for diagnosis of susceptibility to malignant hyperthermia (MH); diagnosis of susceptibility (MH+) or nonsusceptibility (MH-) was made on the basis of in vitro halothane-induced contracture of a separate piece of biopsy. Measurements of ion currents were made at room temperature in the absence of anesthetic agents, using tight-seal whole-cell recording. Fast transient Na+ currents and delayed outward K+ currents were similar in magnitude and kinetics in cells from MH+ and MH- patients. An additional slowly inactivating inward current component was commonly observed in cells from MH+ patients. This current was blockable by tetrodotoxin and was carried by Na+ but not by Ba2+. The component was less frequently observed and was of a lower magnitude in cells from MH- patients. The increased magnitude of the slow inward current observed in cultured muscle cells from MH+ patients may be a manifestation of the lesion that causes MH.
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PMID:Malignant hyperthermia: slow sodium current in cultured human muscle cells. 255 20

1. Diltiazem (10 mumol/L) and verapamil (10 mumol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures. 2. Like the skeletal muscle relaxant dantrolene sodium (6 mumol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine. 3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive. 4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome. 5. These results also suggest an abnormality in transverse tubule-sarcoplasmic reticulum communication.
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PMID:Effect of diltiazem, verapamil and dantrolene on the contractility of isolated malignant hyperpyrexia-susceptible human skeletal muscle. 261 62


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