Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)
 ...
PMID:Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation. 16

This study compares several methods for diagnosing susceptibility to malignant hyperthermia, using two groups of Poland China swine narrowly defined as genetically susceptible or normal (five pigs each) depending respectively on their response to halothane or to halothane and succinylcholine. Vastus medialis muscle biopsies were excised under thiopental-N2O-O2 anesthesia and used for examination of (1) contracture responses to halothane, (2) contracture responses to caffeine and halothane-caffeine, and (3) adenosine triphosphate (ATP) depletion with and without halothane. All studies were performed in organ baths at 37 C. Halothane alone produced contractures in two susceptible and one normal preparation; caffeine always produced a contracture at lower concentrations in susceptible muscle; caffeine-halothane contractures in susceptible muscle occurred at lower mean caffeine concentrations, but there was some overlap of individual values; mean ATP depletion was greater in susceptible muscle, but with considerable overlap. Comparisons with the findings of others were hampered by use of absolute rather than comparative values for tension, e.g., grams, rather than grams per cross-sectional area or fraction of peak tension. Examination of the complete dose-response curve provided the best comparative information and caffeine was the consistent predictor of susceptibility.
 ...
PMID:Muscle contractures and adenosine triphosphate depletion in porcine malignant hyperthermia. 57 59

Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization-induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization-induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm.
 ...
PMID:[The effect of muscle relaxants on masseter tone. An experimental study in an MH-susceptible swine model]. 161 14

We report on the fulminant crisis of malignant hyperthermia occurring in a 30-year-old female during kidney transplantation. In the past, she had been anaesthetised repeatedly without complications. Anaesthesia was induced with thiopental and vecuronium and continued with isoflurane/N2O/O2. After an initially normal course of anaesthesia, the patient developed symptoms of a fulminant malignant hyperthermia (MH) including excessive increase in end expiratory CO2, hyperkalaemia, tachycardia and hyperpyrexia. The patient was saved by the timely administration of dantrolene. A surgical revision required the next day because of bleeding was done under dantrolene cover and took an uncomplicated course. The patient was extubated 7.5 hours after the second intervention and transferred to a normal ward after 4 days. A subsequently performed in vitro contracture test clearly revealed susceptibility to malignant hyperthermia.
 ...
PMID:[Fulminant malignant hyperthermia during the 6th general anesthesia using volatile anesthetics]. 178 10

This report describes a cardiac arrest that occurred in a 4-month-old infant during induction of anesthesia. During the administration of N2O/O2 and halothane via a face mask tachycardia was noted and rigor followed the application of succinylcholine for intubation. Shortly thereafter cardiac arrest occurred; 15 min later we found a profound metabolic acidosis as well as signs of rhabdomyolysis with a serum potassium level of 10.3 mmol/l and an increase in serum creatine kinase (CK). While performing cardiopulmonary resuscitation (CPR) and treating the acid-base imbalance and hyperkalemia, we administered--suspecting malignant hyperthermia (MH)--dantrolene. Approximately 60 min post-arrest we achieved stabilization of the vital signs. During the following hours the CK level rose to 99, 600 IU/l and myoglobinuria of 360,000 micrograms/l confirmed the extent of the rhabdomyolysis. The infant was discharged home without detectable sequelae after 2 1/2 weeks. Comparisons with corresponding case reports in the literature lead to the supposition that our patient suffered from a myopathy thus far undiagnosed. To what extent a MH episode may have contributed to the clinical picture cannot be determined at present. The spectrum of adverse reactions to volatile anesthetics and succinylcholine in patients with myopathic disorders is presented and discussed. As in other case reports, the dramatic course described here also demonstrates that in addition to CPR and treatment of the acid-base and electrolyte imbalances, administration of dantrolene should be considered at an early stage.
 ...
PMID:[Cardiac arrest during anesthesia induction with halothane and succinylcholine in an infant. Massive hyperkalemia and rhabdomyolysis in suspected myopathy and/or malignant hyperthermia]. 195 45

The Authors consider the problems involved in dental treatment of the handicapped patients. Accuracy in diagnosis of the handicap factor, knowledge about its consequences on pathophysiological status and about chronically assumed drugs are the first step: in fact these patients may be affected by a wide variety of physiopathologic and mental diseases. Failure of cooperation requires general anesthesia or sedation techniques. General anesthesia can be dangerous (malignant hyperthermia in myopathies, difficult intubation in facial anomalies, pharmacological interactions); furthermore, its frequent application even in order to perform minimal treatment is often unsuitable. Sedation techniques offer a more convenient possibility, but must be practised by trained operators. Nitrous oxide alone rarely produces in fact a sufficient degree of sedation and is suitable only in patients affected by very slight mental insufficiency. In the other cases, association with various drugs (as benzodiazepines, barbiturates etc) is needed. In such a situation, the active and continuous presence of the anesthesiologist becomes mandatory.
 ...
PMID:[Handicapped patients. General anesthesia or sedation?]. 214 46

The Authors, after a brief review of malignant hyperthermia (MH), describe the use of NLA a Harrington's surgical procedure in a malignant hyperthermia susceptible (MHS) patient. Such an anaesthesiological procedure, using benzodiazepines, droperidol, fentanyl, pancuronium and N2O/O2, didn't lead to any form of MH crisis on to complications.
 ...
PMID:[Use of neuroleptoanesthesia for carrying out a Harrington intervention in a patient probably susceptible to malignant hyperthermia]. 263 80

A 7-day-old male newborn developed malignant hyperthermia postoperatively (uncomplicated surgical reposition of a local skull impression caused by birth trauma; general anesthesia with succinylcholine and halothane/N2O). The clinical course was typical (body temperature up to 43.7 degrees C) and led to death 30 h after anesthesia. It is emphasized that malignant hyperthermia may occur unexpectedly in the postoperative period, so that all medical personnel on surgical wards, especially in pediatrics, should be able to diagnose this life-threatening disease as soon as possible and provide adequate therapy with dantrolene.
 ...
PMID:[Postoperative malignant hyperthermia in a 7-day-old infant?]. 292 69

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2 greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/l, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/l. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2 X min-1 X kg-1 when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4-8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.
 ...
PMID:Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine. 307 72

To elucidate a pathogenesis for the reduction in bone calcium content observed in MHS individuals, we studied the acute calcium homeostasis of MHS swine. This was achieved by the serial measurement, with a calcium selective electrode, of calcium transients in Landrace MHS (five) and control Landrace/large white cross MH negative (five) swine following IV bolus injection of calcium gluconate 0.1 mmol X kg-1--a dose which induced an acute 45 per cent increase in plasma ionised calcium. Experimental animals were anaesthetised with ketamine 10 mg X kg-1 IM, thiopentone (intermittent divided doses) 15-25 mg X kg-1 (total) IV and N2O/O2 (FIO2 0.3) by IPPV to maintain a normal blood gas, acid/base state. The plasma ionised calcium decay curve observed in MHS swine did not differ from that of control normal swine. Further it was noted that the induced acute rise in plasma ionised calcium failed to trigger the MH syndrome in any MHS swine. It is concluded that the mechanisms of acute calcium homeostasis in MHS swine are normal. An explanation for the reduction in bone calcium content observed in MHS individuals must be sought, therefore, through study of the slow long-term component of the calcium regulatory process. In addition, the conventional strictures placed on the use, in MHS patients, of calcium gluconate are called in question.
 ...
PMID:Acute calcium homeostasis in MHS swine. 360 54


1 2 Next >>