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)

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.
Arch Mal Coeur Vaiss 1985 Dec
PMID:[In vitro electrophysiological effects of sodium dantrolene on isolated preparations of Purkinje fibers and ventricular myocardium of sheep]. 242 77

The relationship between the graft-versus-host reactivity of lymphocytes from F2 hybrid and backcross rats and their susceptibility to inter-parental strain alloantisera has been investigated. Apart from associations between the immunological responsiveness of individual rats and the extent of alloantiserum susceptibility of their lymphocytes, selective reactivity of groups of lymphocytes that were separable from the general population by means of their alloantiserum susceptibility was observed. Those host lymphocytes which expressed a preponderance of DA-derived determinants were preferentially implicated in graft-versus-host reactions elicited by PVG lymphocytes in (PVG X DA)F2 hybrid rats. The anti-(PVG X DA)F1 hybrid reactivity of some (PVG X F1) backcross rats was selectively concentrated in that fraction of the lymphocyte population which expressed the highest levels of PVG-derived determinants. It is proposed that heterogeneously expressed MHS determinants may have a role in regulating selective participation by subpopulations of lymphocytes in allogeneic reactions.
Aust J Exp Biol Med Sci 1985 Dec
PMID:The relationship of the antigenic determinants expressed by rat lymphoid cells to their participation in graft-versus-host reactions. 242 2

Fifteen crossbred pigs of Swedish Landrace and Yorkshire, about 6 months of age and susceptible to develop malignant hyperthermia (MH) when exposed to halothane, were subjected to stress provoked by the myorelaxant succinylcholine. The results were compared with those of 12 normal pigs. During the stress the halothane-sensitive (HS) pigs showed much higher levels of plasma noradrenaline and adrenaline and more severe ventricular arrhythmias than the controls. The degree of myocardial degeneration and necrosis being similar to catecholamine induced myocardial damage was significantly higher in the HS pigs than in the controls. The ultrastructural examination revealed three main types of changes in affected myocardial cells. One type of myocardial cell damage was characterized by various degree of hypercontraction, enlarged mitochondria with dense bodies and dilated sarcoplasmic reticulum. The other type showed mitochondria with tubular configuration whereas the third type of cell damage was characterized by almost normal mitochondria combined with a severe damage of the myofilaments. Three HS pigs which died within 30 min after stress showed signs of malignant hyperthermia. No signs of the disease were observed in the other 12 HS pigs.
Zentralbl Veterinarmed A 1989 Dec
PMID:Cardiac manifestation and blood catecholamine levels during succinylcholine-induced stress of malignant hyperthermia sensitive pigs. 251 87

Since ketamine has been incriminated as triggering malignant hyperthermia (MH) [3, 9, 13, 14, 18], but has still been used uneventfully in MH susceptible patients, we performed an in vitro study to examine the safety of ketamine for use in human MH. METHODS. Muscle specimens of 20 patients who had muscle biopsies to diagnose MH were investigated. In every patient diagnostic contracture tests (2 halothane (Hal) and 2 caffeine (Caf) were done according to the protocol established by the European MH group (EMHG). In addition, one test unit for investigating the effect of stepwise increased bath-concentrations of ketamine (5, 10, 20, 60, 120, 240 and 960 mumol/l) and a further one serving as control (no drugs added to the bath) were used. Combined Hal (2 vol%) and Ket (960 mumol/l) tests were performed in 9 patients (4 MHS, 4 MHN, 1 MHEh). Changes in baseline contractures and mechanical twitch tension were evaluated. RESULTS. The diagnostic test showed MHS in 8, MHN in 8 and MHEh in 4 patients. Ketamine did not induce baseline contractures in any of the tests performed. Contractures induced by 2 vol% of halothane in 4 MHS muscles did not change significantly when ketamine was added to the bath (concentration 960 mumol/l). A significant, dose-related decrease in mechanical twitch tension occurred, when ketamine was added to the test. At the highest concentration (960 mumol) twitch tension was reduced by 55%. Twitch tension remained stable in untreated muscles. No significant differences were found between the specimens from MHS, MHN and MHE patients. This reduction in twitch tension was more pronounced in specimens exposed to both halothane (2 vol%) and ketamine (960 mumol/l), resulting in an average decrease of 71%. CONCLUSION. In accordance with Fletcher et al., our results indicate that ketamine - at least in vitro - does not trigger MH. In MHS muscles, ketamine does not augment halothane-induced baseline contractures. The ketamine-induced reduction of mechanical twitch tension in directly stimulated human muscles has not been described before. Analogous findings in frog sartorius muscles can be found in the literature. Whereas the effect of ketamine on indirectly stimulated muscle has been investigated by several authors, the underlying mechanism of ketamine-induced twitch suppression in directly stimulated muscles is not known. Inhibition of calcium release from or accelerated uptake into the sarcoplasmatic reticulum have been reported.
Anaesthesist 1989 Dec
PMID:[The action of ketamine on muscle contractile behavior. In vitro studies on the musculature of subjects susceptible to malignant hyperthermia]. 261 30

Mechanisms and their pharmacology of Ca ion mobilization in skeletal, cardiac and smooth muscles are reviewed. In skeletal muscle, it is very likely that depolarization of T-tubule membrane causes conformational changes of dihydropyridine (DHP) receptors in the T-membrane, which in turn, most probably through some kind of protein-protein interaction, open the Ca2+ release channel in the sarcoplasmic reticulum (SR), the ryanodine receptor. Both the DHP receptor and ryanodine receptor have already been purified and sequenced, but the nature of the information transduction between these proteins still remains to be solved. Both of these proteins appear to have dual functions: the DHP receptor as a voltage sensor as described above and as a voltage-dependent Ca2+ channel and the ryanodine receptor as a physiological Ca2+ release channel and as a Ca2(+)-induced Ca2+ release (CICR) channel, an abnormality of which is known to cause malignant hyperthermia. In cardiac muscle, Ca2+ influx is essential not as the main Ca2+ source but to release Ca2+ from the SR, probably not through the CICR mechanism in the narrow sense but through a mechanism dependent on both Ca2+ and T-tubule depolarization. Several mechanisms of Ca2+ mobilization are used in smooth muscles and their features, different from those in striated muscles, are briefly reviewed.
Nihon Yakurigaku Zasshi 1989 Dec
PMID:[Mechanisms and their pharmacology of mobilization of calcium ion in muscle cells]. 269 57

Though a malignant hyperthermia (MH) crisis is still a critical event during general anesthesia, recent developments in prophylaxis and treatment should help in avoiding fatal episodes. The best means to avoid MH episodes would be early recognition of MH susceptibility. Today the only reliable test to identify MH susceptibility is the in vitro contracture test. Thus, to diagnose MH susceptibility we performed this test on muscle biopsies from 26 individuals who: (1) had an event during general anesthesia that may have been indicative of MH (4 patients); (2) had a family member with a medical history of MH (20 patients); or (3) had unexplained elevated CK levels (1 patient). The criteria according to which patients were submitted to the testing are shown in detail in Table 1. We used the standardized version of the contracture test that has been proposed by the European Malignant Hyperpyrexia Group. Muscle biopsies (20-30 mm long, 8 mm diameter) were dissected into 8-10 small bundles (2-3 mm diameter) and tested within 3 h post-biopsy in four independent tissue baths with various concentrations of caffeine or halothane. According to the concentration of caffeine or halothane necessary to elicit contractures exceeding a predefined force threshold (20 mN), it was possible to classify the patients as MHS (MH-susceptible), MHE (equivocal), or MHN (negative). In addition to the in vitro test, clinical, laboratory, and neurophysiological data were collected from these patients and correlated with the individual test results (Table 2). Thirteen patients were classified as MHS, five were MHE, and seven patients MHN (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)
Anaesthesist 1987 Dec
PMID:[Diagnosis of susceptibility to malignant hyperthermia using the in vitro contracture test]. 283 Aug 5

The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of antipsychotic drugs. It is characterized by severe muscular rigidity, hyperthermia, and autonomic disturbances. Neuroleptic malignant syndrome is easily confused with other health problems; distinctions between it and malignant hyperthermia, heatstroke, and lethal catatonia are made. The relevant literature is reviewed; a case history is presented; and implications for nursing care (e.g., early detection) are discussed.
J Neurosurg Nurs 1985 Dec
PMID:Neuroleptic malignant syndrome. 286 79

To investigate possible abnormalities in erythrocyte membrane enzyme activities in the pharmacogenetic disorder MH, membrane ATPase activities have been examined in erythrocyte ghosts prepared from red blood cells of MHS and normal swine. While no differences were noted in Mg2+-ATPase activities, the (Na+, K+)-ATPase activity of MHS erythrocyte ghosts was less than that of normal ghosts. Ca2+-ATPase activity exhibited low- and high-affinity Ca2+-binding sites in both types of erythrocyte ghost. While the Km for Ca2+ was greater for normal than for MHS erythrocyte ghosts at the high-affinity Ca2+-binding site, the reverse was true at the low-affinity Ca2+-binding site. Irrespective of the type of calcium binding site occupied, the Vmax for normal erythrocyte ghost Ca2+-ATPase activity was greater than that for MHS ghosts. In the presence of calmodulin, there was now no difference between MHS and normal erythrocyte ghosts in either the Km for Ca2+ or the Vmax of the Ca2+-ATPase activity. To determine if the calcium pumping activity of intact MHS and normal pig erythrocytes differed, calcium efflux from the 45Ca-loaded erythrocytes was determined; this activity was significantly greater for MHS than for normal erythrocytes. Thus, the present study confirms that there are abnormalities in the membranes of MHS pig red blood cells. However, we conclude that these abnormalities are unlikely to result in an impaired ability of MHS erythrocytes to regulate their cytosolic Ca2+ concentration.
Biochem Med Metab Biol 1987 Dec
PMID:Erythrocyte membrane ATPase and calcium pumping activities in porcine malignant hyperthermia. 296 54

Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.
Anesthesiology 1988 Dec
PMID:Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients. 305 38

Malignant hyperthermia (MH) is a genetic disease in man and other animal species that predisposes to a catastrophic hypermetabolic syndrome that is triggered by certain anesthetic agents. A working hypothesis is that a defect in regulation of muscle cell calcium is the primary mechanism that initiates the MH syndrome. This paper reviews the evidence for a defect in muscle cell calcium as regulated by the sarcoplasmic reticulum membrane system. Skeletal muscle biopsied from MH man, pigs and dogs has abnormal in vitro contracture response to halothane and caffeine and these responses can be altered by lowering calcium content of the bathing solution and/or the muscle. Measurements of MH muscle cell Ca2+ by Ca2+-specific microelectrodes in vivo and fura-2 in vitro have demonstrated abnormal Ca2+ levels in resting and in caffeine-stimulated states. The SR membrane system is the primary calcium regulating organelle in skeletal muscle and a likely site for the defect in MH muscle. Two Ca2+ regulating functions of the SR have been explored in SR isolated from MH muscle. An abnormality of the 100K Ca2+-ATPase protein that functions to transport Ca2+ from myoplasm to inside the SR does not appear to be responsible for MH. The most probable defective site in the SR appears to be Ca2+ release channels and a Ca2+-induced Ca2+ release pathway has been shown to be abnormal in SR from MH human and pig muscle.
Cell Calcium 1988 Dec
PMID:SR function in malignant hyperthermia. 306 91


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