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)

We encountered a case of malignant hyperthermia caused by intravenous lidocaine which had been administered as treatment for a ventricular arrhythmia. The patient, a 72-year-old male, was admitted with chronic renal failure and aortic valvular stenosis. His chronic renal failure progressed, and congestive heart failure developed, and ventricular arrhythmias occurred frequently. For the treatment of these arrhythmias, lidocaine was injected and continuous infusion was started. Despite initial improvement in symptoms and laboratory data following hemofiltration, refractory ventricular tachycardia occurred. The patient was treated with large doses of lidocaine. His body temperature rose to a maximum of 41.7 degrees C, and generalized muscular twitching was observed before he lost consciousness. Serum and urinary myoglobin levels became elevated. This abnormally high fever was relieved only by dantrolene sodium. After we made a diagnosis of malignant hyperthermia and stopped the lidocaine infusion, the high fever resolved quickly. It is important to note that malignant hyperthermia can be caused by lidocaine and amide-linked local anesthetics.
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PMID:Malignant hyperthermia caused by intravenous lidocaine for ventricular arrhythmia. 147 68

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.
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PMID:[The action of ketamine on muscle contractile behavior. In vitro studies on the musculature of subjects susceptible to malignant hyperthermia]. 261 30

A noninvasive method to diagnose malignant hyperthermia (MH) was sought. To this end, in vivo isometric twitch properties of the ankle dorsiflexor muscles were studied in three groups: (1) MH-susceptible patients (n = 12), (2) relatives (n = 12) of MH-susceptible patients who were judged to be MH resistant, and (3) a group of normal volunteers (n = 42) chosen from the community. Twitch properties were studied under resting state conditions and with 1 or 2 Hz stimulation to produce the negative staircase twitch response. There was a high degree of overlap between the ranges of the measured twitch parameters of all groups. Thus, the techniques presented in this study have no value in diagnosing susceptibility to MH. Several physiological features of human isometric twitch properties were demonstrated: (1) slowing of twitch speed with advancing age, (2) strong positive correlation between body weight and twitch torque, and (3) a negative staircase response typical of that described in other mammalian twitch studies.
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PMID:Ankle dorsiflexor twitch properties in malignant hyperthermia. 271 Jan 44

In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown that serotonin (5-HT2) receptor agonists can induce MH and "psychotic" behaviour. Both can be prevented by 5-HT2 receptor antagonists. Furthermore, free levels of serotonin in plasma increased concomitantly with clinical and laboratory parameters during halothane-induced MH in pigs. In this study the in vitro-effects of the 5-HT2 receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and normal (MHN) patients. METHODS. Muscle biopsies were obtained from 37 patients aged 5-69 years (23.6 +/- 5.3 years) with clinical suspicion for MH. The patients were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the DOI study. DOI was added to the organ bath in a concentration of 0.02 mmol/l. The in vitro effects on contracture development and muscle twitch were observed for 120 min. RESULTS. Muscle specimens of all patients developed contractures after administration of DOI. However, DOI produced an earlier development of contracture in MHS (17.0 +/- 1.8 min; n = 17) than in MHN (64.7 +/- 5.9 min; n = 15) muscles. In MHS muscles, contractures were more distinct than in MHN muscles; at the end of the experiment, contractures had reached a maximum of 12.5 +/- 0.9 mN in MHS and 5.1 +/- 0.7 mN in MHN muscles. Muscle twitch following DOI administration was reduced significantly in both MHS and MHN muscles. The results of four MHE muscles were comparable with MHS. CONCLUSION. The present study supports the assumption that an altered serotonin system might be involved in the development of MH. In further studies it should investigated whether 5-HT2 receptors of skeletal muscles from MHS subjects are disordered in function or structure. 5-HT2 receptor agonists should be considered as MH-triggering agents.
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PMID:[Effects of serotonin 2 receptor agonists on skeletal muscle preparations in patients with a disposition toward malignant hyperthermia]. 757 1

Important aspects of the excitation-contraction (EC) coupling process in skeletal muscle have been revealed using mechanically-skinned fibers in which the transverse-tubular system can be depolarized by ion substitution or electrical stimulation, activating the voltage-sensors which in turn open the Ca2+ release channels in the adjacent sarcoplasmic reticulum (SR). Twitch and tetanic force responses elicited in skinned fibers closely resemble those in intact fibers, showing that the coupling mechanism is entirely functional. It was found that ATP has to be bound to the Ca2+ release channels for them to be activated by the voltage-sensors and that the coupling mechanism likely involves the voltage-sensors removing the inhibitory effects of cytoplasmic Mg2+ on the release channels; such findings are relevant to the basis of muscle fatigue and to certain diseases such as malignant hyperthermia (MH). EC coupling is evidently not mediated by upmodulation of Ca2+-induced Ca2+ release (CICR) or by an oxidation or phosphorylation reaction. The Ca2+ load in the SR of skinned fibers can be set at the endogenous level or otherwise. The normal coupling mechanism functions well in mammalian fast-twitch fibers even when the SR is only partially loaded, whereas CICR is highly dependent on SR luminal Ca2+ and caffeine is poorly effective at inducing release at the endogenous SR Ca2+ load level.
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PMID:Voltage-sensor control of Ca2+ release in skeletal muscle: insights from skinned fibers. 1189 57