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)

Halothane in concentrations exceeding 1.2 mmol litre-1 increased (P less than 0.05) the apparent intracellular concentration of calcium in lymphocytes from 12 patients being tested for susceptibility to malignant hyperthermia (MH) using the fluorescent Ca2+ indicator, fura2. There was no difference in [Ca2+]i between lymphocytes from patients found to be MH susceptible (n = 5) on in vitro contracture testing with halothane and caffeine and those from MH negative patients (n = 6). Thus determination of [Ca2+]i in lymphocytes after exposure to halothane could not be used as a diagnostic test for MH susceptibility.
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PMID:Cytosolic free calcium concentrations in lymphocytes from malignant hyperthermia susceptible patients. 232 83

This investigation sought to determine if the Ca2+ antagonist, TMB-8, alters the contracture responses of malignant hyperthermia susceptible (MHS) skeletal muscle to halothane and to caffeine. Muscle fiber bundles were excised from both MHS and normal pigs and exposed to TMB-8 (100 microM), halothane (3%) and caffeine (0.5-8.0 mM), administered alone and in combination. TMB-8 depressed tension developed during isometric twitches in both MHS and normal muscle but had no effect on resting tension (RT). Halothane, however, increased RT in MHS but not in normal muscle. TMB-8 failed to reduce the halothane contracture of MHS muscle but hastened its onset. Caffeine concentrations of greater than or equal to 2 mM increased RT in MHS whereas only 8 mM evoked contracture of normal muscle. These effects were also unaltered by TMB-8. Results suggest that TMB-8 does not inhibit halothane nor caffeine contractures of MHS muscle.
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PMID:Effects of the calcium antagonist, TMB-8 on halothane and on caffeine contractures of malignant hyperthermia susceptible skeletal muscle. 238 62

Transverse tubule (TT) calcium transport and permeability were examined in the inherited skeletal muscle disorder malignant hyperthermia (MH). ATP-dependent calcium uptake by TT vesicles isolated from normal and MH-susceptible (MHS) pig muscle had a similar dependence on ionized Ca2+ concentration (K1/2 for Ca2+ of 0.21 +/- 0.04 and 0.25 +/- 0.05 microM for MHS and normal TT, respectively), as well as a similar Vmax (20.9 +/- 2.0 and 23.7 +/- 4.5 nmol Ca/mg protein/min for MHS and normal TT, respectively). Furthermore, the stimulation of calcium uptake by either calmodulin or cAMP-dependent protein kinase was similar in normal and MHS TT. Halothane concentrations greater than 2 mM inhibited calcium uptake by either normal or MHS TT to a similar extent (IC50 = 8 mM). Dantrolene (10 microM), nitrendipine (1 microM), and Bay K 8644 (1 microM) had no significant effect on either the initial rates of calcium uptake or maximal calcium accumulation of either MHS or normal TT vesicles. However, in the absence of any added agents, maximum calcium accumulation by MHS TT was significantly less than by normal TT (90 +/- 10 versus 130 +/- 9 nmol Ca/mg protein after 15 min of uptake). This difference was not due to an increased permeability of MHS TT to calcium, nor was it due to a difference in the sarcoplasmic reticulum contamination (less than 5%) of the MHS and normal preparations. Although our results indicate there is no significant defect in MHS TT calcium regulation, the diminished maximum calcium accumulation by MHS TT may contribute to the abnormal sarcoplasmic calcium homeostasis in skeletal muscle during an MH crisis.
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PMID:Transverse tubule calcium regulation in malignant hyperthermia. 253 1

In both control pigs and pigs susceptible to malignant hyperpyrexia (MH), the size of the calcium current (ICa) and the amount of asymmetric charge movement varied considerably between different gracilis muscle fibers but appeared to vary in parallel. The mean amount of both ICa and charge movement were slightly but significantly smaller in MH-susceptible (MHS) muscle compared with normal muscle. Halothane (1% v/v) reduced both parameters by almost 50%. One interpretation of the data is that the signal, which couples depolarization to calcium release from the sarcoplasmic reticulum, is abnormal in MHS muscle.
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PMID:Calcium currents and asymmetric charge movement in malignant hyperpyrexia. 254 Apr 32

The sarcoplasmic reticulum from muscle of swine which are susceptible to malignant hyperpyrexia is deficient in inositol 1,4,5-trisphosphate phosphatase (InsP35-ase) activity, which leads to high intracellular concentrations of inositol 1,4,5-trisphosphate (InsP3) and of calcium ions. Halothane inhibits InsP35-ase and further increases myoplasmic InsP3 and calcium ion concentrations, and produces the clinical features of malignant hyperpyrexia.
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PMID:Inositol 1,4,5-trisphosphate phosphatase deficiency and malignant hyperpyrexia in swine. 256 94

A 6 month old domestic shorthaired cat died of suspected malignant hyperthermia. Anesthesia was induced and maintained with halothane vaporized in oxygen and nitrous oxide, after acepromazine premedication. Before an incision was made, the cat's heart rate dropped from 140 to 90 beats/min concomitant with a drop in blood pressure. Glycopyrrolate administration resulted in severe ventricular tachycardia (340 beats/min). Halothane and nitrous oxide were discontinued and the surgery was abandoned. Lidocaine administration resulted in a normal sinus rhythm. In recovery, the cat was tachypneic and struggling, with a rectal temperature of 40.1 degrees C that quickly increased to 41.4 degrees C. While the cat was being cooled, cardiac dysrhythmias progressed to ventricular fibrillation that was not responsive to cardiorespiratory resuscitation. Blood specimens obtained while the cat was being cooled showed hyperkalemia (10.0 mEq/L) and increased serum creatine kinase activity (780 IU/L). There was extreme extensor rigidity (rigor mortis) within 5 min of cardiac arrest. Results of microscopic and electron microscopic examination of muscle showed occasional perivascular infiltrates of lymphocytes with infrequent perimysial and epimysial neutrophils and a few sarcomeres with streaming of Z-bands (suggesting a contracted state). Histochemical evaluation of skeletal muscle showed no significant difference between type I and type II fibers.
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PMID:Suspected malignant hyperthermia after halothane anesthesia in a cat. 260 80

Malignant hyperthermia, a disorder of uncertain genetic transmission related to use of certain anesthetics and muscle relaxants, is uncommon and potentially fatal. It has been most commonly linked to succinylcholine chloride (Anectine, Quelicin, Sucostrin) and halothane (Fluothane). The most important treatment method, after discontinuation of the triggering agent(s), is immediate administration of dantrolene sodium (Dantrium). Diagnostic testing of susceptibility is available but has significant limitations. If the new phosphorus nuclear magnetic resonance spectroscopy proves to be an accurate test for susceptibility and becomes more readily available, decreases in the current case-fatality rate of 10% may follow.
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PMID:Malignant hyperthermia. Quick recognition and treatment to avoid death. 272 33

In this study we report on the effect of halothane exposure on the skeletal muscle membrane and calcium localization in 9 patients with confirmed susceptibility to malignant hyperthermia and compare them with 11 non-susceptible cases of malignant hyperthermia. Two normal muscle specimens with physiologically induced muscle contractures were also included for comparison. Halothane exposure in malignant hyperthermia-susceptible cases showed severe muscle contractures, definite breaks in the plasma membrane with peroxidase penetration, and large number of calcium granules within the mitochondria and sarcoplasmic reticulum. Malignant hyperthermia-non-susceptible cases and muscle with physiological contractures did not show discontinuity of the plasma membrane or excessive calcium deposits. Based on these findings we conclude that the halothane exposure in malignant hyperthermia-susceptible patients causes breaks in the muscle plasma membrane.
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PMID:Membrane abnormality in malignant hyperthermia. 273 91

Halothane-induced malignant hyperthermia (MH) is thought to result from a defect in the regulation of cytosolic calcium concentration in MH-susceptible (MHS) skeletal muscle. Such a defect might be expected to alter the time course of contractile responses. To test this hypothesis, isolated intact cell bundles from external intercostal and common digital extensor muscles of normal and MHS pigs were stimulated electrically to elicit twitch and tetanic tension in the presence and absence of halothane (2.5%). Time intervals measured for both twitches and tetani were (1) the latent period between the stimulus and tension increase, (2) the time to peak tension, and (3) the half-relaxation time. In contrast to previous reports, halothane had no effect on any measured time course parameter of twitches of either type of normal or MHS muscle, nor did the twitches of MHS and normal muscles differ in any parameter in the absence of halothane. However, the tetanic tension relaxation in both types of MHS muscle was markedly slowed by halothane, whereas in normal muscles there was little change. The slower rate of relaxation induced by halothane in MHS muscles suggests that halothane, either directly or indirectly, enhances the release or slows the removal of calcium in intact MHS muscles following maximal activation. This slowed tetanus relaxation could be of use in identification of MHS individuals.
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PMID:Porcine malignant hyperthermia: halothane effects on force generation in skeletal muscles. 274 37

Myoballs were cultured from biopsies of adult human skeletal muscle. Transient currents through the sodium channels were elicited by depolarizing a myoball membrane with the whole-cell patch-clamp technique. The properties of the sodium channels were determined from the Hodgkin-Huxley parameters (INa max, tau m, tau h, h infinity-curve) derived from these transients. Halothane, when applied at 3.4 mmol/l (approximately 15 kPa), blocked about 50% of the current through the adult, TTX-sensitive sodium channels but had little effect on the current through the juvenile, TTX-insensitive sodium channels. At greater than 12 mmol/l, halothane blocked both channel types completely. The time constants of activation and inactivation were decreased in the presence of 3.4 mmol/l halothane but not enough to account for the decrease of the current amplitude. Halothane shifted the h infinity-curves of both channel types toward more negative potentials by an amount that was roughly proportional to its concentration. Myoballs from a man susceptible to malignant hyperthermia (MH) gave the same results as the controls indicating that the halothane effect on the action potential of MH-susceptible muscle are not mediated by a specific effect on the sodium channels.
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PMID:Differential effects of halothane on adult and juvenile sodium channels in human muscle. 284 55


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