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)

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane-susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH-susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity.
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PMID:Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome. 142 16

Tonsillectomy in adults and older children is typically accompanied by 7 to 14 days of pain. On the basis of clinical observations of patients treated perioperatively with dantrolene sodium for malignant hyperthermia, we hypothesized that pharyngeal muscle spasms are a major factor in tonsillectomy pain. We entered 113 patients, 11 years of age and older, into a double-blind, placebo-controlled study to evaluate the effectiveness of dantrolene sodium in reduction of tonsillectomy pain. Patients were randomly assigned either dantrolene (1.5 mg/kg per day) or placebo orally four times a day for 5 days postoperatively. On a standardized questionnaire, the patient recorded pain, diet, activity level, analgesics, and side effects, daily for 2 weeks. Also, alkaline phosphatase (alk phos) and serum aspartate aminotransferase (SGOT) levels were determined before the operation and 2 weeks after. Patients who received dantrolene had no significant differences in subjective pain, diet, or activity level scores from those of patients who received placebo. Dantrolene patients did, however, require significantly less analgesic use than placebo patients (p = 0.034, 0.015, and 0.005 for postoperative days 2, 3, and 4, respectively). There was no significant difference in side effects or changes in liver enzyme between the dantrolene and placebo groups. We conclude that dantrolene sodium, given in the dosage noted, is effective in reduction of analgesic requirements after tonsillectomy.
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PMID:Oral dantrolene sodium for tonsillectomy pain: a double-blind study. 312 47

Malignant hyperthermia (MH) is a naturally occurring disease of stress-susceptible (SS) pigs subjected to triggering agents or stress. MH is characterized by accelerated muscle metabolism and hyperthermia due to abnormally increased myoplasmic Ca2+ levels. Dantrolene is used for the treatment of MH and acts by reducing the myoplasmic Ca2+ levels. Muscle lesions can be induced by experimental restraint stress in SS pigs and are suspected to be caused by increased myoplasmic Ca2+ levels. This experiment was performed in order to study if stress induced muscle lesions could be reduced by dantrolene. Nine SS pigs were exposed to experimental restraint stress provoked by a 12 min intravenous (i.v.) infusion of the depolarizing myorelaxant succinylcholine. Five pigs were orally dosed with dantrolene (5 mg/kg), twice, about 24 and 5 h before the stress (group A). The other four pigs were treated with a single i.v. infusion of dantrolene (5 mg/kg), 30 min before stress (group B). The animals were necropsied approximately 48 h after the stress and 24 skeletal muscles were examined macro- and microscopically. No clinical signs of MH occurred during the experiment. The required dose of succinylcholine was higher in group B (0.08 mg/kg/min) than in group A (0.03 mg/kg/min) indicating decreased sensitivity to succinylcholine in SS pigs after i.v. treatment with dantrolene. The pigs in group A, but not in group B showed slightly increased serum levels of creatine kinase (CK) and aspartate aminotransferase (ASAT) at time of necropsy. A significant reduction in acute muscle lesions was observed in both groups, especially in group B, when compared with SS pigs subjected to restraint stress, but not treated with dantrolene. The muscle lesions induced by the stress model are considered to be induced by increased myoplasmic Ca2+ levels since they can be reduced by dantrolene treatment.
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PMID:The reduction of skeletal muscle lesions after experimental stress in stress-susceptible pigs protected with dantrolene. 882 90

Fifteen related dogs were studied for susceptibility to malignant hyperthermia using halothane challenge and caffeine contracture tests. These dogs had hypertrophied muscles, were of a nervous temperament and had rectal temperatures at the upper limit of the normal range. Clinical pathology findings were mild elevations of serum aspartate transaminase and mean corpuscular hemoglobin. In vitro caffeine contracture tests were performed on muscle biopsies from five of these dogs. The concentration of caffeine required to increase resting tension by 1 g in biopsy specimens of these dogs was significantly lower than that required for control dogs: 7.6 +/- 1.38 (x +/- SEM) versus 15.5 +/- 2.52 mM (P < 0.025), and in the presence of 1% halothane, 3.6 +/- 1.44 versus 10.6 +/- 2.19 mM (P < 0.05). Internal nuclei, fiber caliber variation and fiber hypertrophy were found in histological studies of muscle biopsies. Two other dogs possibly died of a canine stress syndrome analagous to the porcine stress syndrome which occurs in malignant hyperthermia susceptible swine. Eight others of this family were anesthetized with halothane or methoxyflurane. Methoxyflurane did not trigger the syndrome. The first exposure to halothane caused death from malignant hyperthermia in two dogs and a third died on the second exposure to halothane. Postmortem findings were nonspecific. The other three dogs exposed to halothane recovered uneventfully. Inheritance of the defect conforms to a multifactorial pattern, with gradations of susceptibility.
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PMID:Canine malignant hyperthermia: diagnosis of susceptibility in a breeding colony. 1742 67