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)

The effect of the intravenous administration of dantrolene 3.5 mg/kg body weight on leg metabolism during porcine malignant hyperthermia (MH) was investigated in six Pietrain pigs. Arterial pH improved only slowly after dantrolene and was associated with the continuing efflux of lactate from the leg. Oxygen uptake by the leg had returned to control values 30 minutes after dantrolene. Glucose production by the leg was observed during malignant hyperthermia but this was rapidly abolished by dantrolene. It is concluded that the most useful indices for assessing the adequacy of the treatment of MH are those which reflect changes in oxidative muscle metabolism.
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PMID:Effect of dantrolene on leg metabolism in porcine malignant hyperthermia. 718 Oct 63

Resting metabolic rate and the energy cost of performing a specific (light work load on a bicycle ergometer were measured in nine subjects susceptible to malignant hyperpyrexia (MHS) and nine control subjects, both fasting and following a 600-kcal meal. Blood glucose, lactate, pyruvate and serum triglycerides, thyroxine, cortisol, creatine kinase, growth hormone, and calcium and potassium levels at rest and immediately following exercise, after fasting and eating, were measured. There was no evidence of increased heat production in the MHS subjects compared with controls. The MHS subjects, however, showed a complete absence of dietary-induced thermogenesis with exercise. Compared with the controls, MHS subjects had higher insulin levels for essentially the same blood glucose values. Triglycerides in the MHS group rose steadily over the course of the experiment, whereas in the controls they did not vary from the initial value. Lactate did not rise as much with exercise in the MHS group but did nor fall with rest, and pyruvate did not change from resting fasting values, whereas in the controls it rose steadily. Differences were also found in thyroxine and cortisol levels between the MHS and control groups. The shunting of blood away from thermogenic tissue is suggested as a mechanism for the absence of diet-induced thermogenesis with exercise in the MHS group and the possibility of an underlying abnormality of cardiovascular (sympathetic) control mechanisms in these subjects is discussed. The biochemical abnormalities are discussed in relation to previous biochemical data from MHS humans and pigs and in relation to the abolition of dietary-induced thermogenesis.
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PMID:Metabolic rate and blood hormone and metabolite levels of individuals susceptible to malignant hyperpyrexia at rest and in response to food and mild exercise. 724 57

Intracellular free calcium is believed to play a major role in the ischaemic cascade which leads to cell death. Calcium channel blockers, which in part inhibit the influx of extracellular calcium, have been shown to be neuroprotective in both complete and focal cerebral ischaemia models. Dantrolene, an agent used in the treatment of malignant hyperthermia, is known to inhibit the release of stored intracellular calcium. Assuming that reduced levels of intracellular free calcium would improve neurologic outcome, we studied the neuroprotective potential of dantrolene. A complete cerebral ischaemia model was used to examine ten anesthetized dogs. Five were given intravenous dantrolene and five were given equal volumes of saline prior to the ischaemic event. Simultaneous occlusion of the venae cavae and ascending aorta provided eleven minutes of complete cerebral ischaemia as monitored by electroencephalography. Arterial blood gases and serum glucose levels were drawn prior to ischaemia, 5 and 20 minutes post-ischaemia, and following extubation. Forty-eight hours following the ischaemic event, neurologic outcomes were scored. No significant differences were observed between the two groups. All ten dogs had equally significant increases in serum glucose levels at 5 and 20 minutes post-ischaemia. The average neurologic outcome of the five dantrolene-treated dogs equalled the average of the five controls. These results suggest that dantrolene, alone, is not neuroprotective during complete cerebral ischaemia.
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PMID:No dantrolene protection in a dog model of complete cerebral ischaemia. 809 51

The halothane test was performed under different conditions in 10 halothane-sensitive growing pigs (Landrace, line 01). Haematological and metabolic changes in blood were monitored during the handling of the pigs before the test, during the exposure to halothane and thereafter. Already in connection with the catching and fixation of the pigs, the levels of haemoglobin in blood, and of glucose, lactate and potassium in plasma increased significantly. However, the concentration of glycerol was not raised before the occurrence of the malignant hyperthermia. While the level of potassium decreased already from the beginning of the halothane exposure until the development of symptoms, the values of haemoglobin, glucose and lactate continued to increased. The level of the free fatty acids did not show any changes during the experimental period. An infusion of phentolamine reduced the increase of haemoglobin and potassium and an infusion of propranolol reduced the increase of haemoglobin and glycerol significantly, without any effect on the result of the halothane test. By an anaesthesia, starting 30 minutes before the exposure to halothane, the development of the typical halothane reaction was obviated for at least 10 minutes. Observed metabolic changes during a simultaneous epinephrine administration were exclusively due to its adrenergic effects.
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PMID:[The effect of anesthesia, of an alpha or beta adrenergic blockade in conscious and of adrenaline in anesthetized halothane-positive swine on hematologic and metabolic parameters in the blood during the course of halothane exposure]. 812 1

Three months before this study, susceptibility for malignant hyperthermia (MH) had been tested in 15 pigs. In all pigs, MH was triggered by administration of 1% halothane. Brain electrical activity was examined during therapy of MH with and without administration of dantrolene. From the EEG, power densities in selected frequencies and the median frequency of the power spectrum were calculated. Therapy was started when severe respiratory changes were observed (PaCO2 > 10 kPa, mixed venous oxygen tension (PvO2) < 4 kPa). At this time, heart rate exceeded 150 beat min-1, mean arterial pressure (MAP) was less than 60 mm Hg and median frequency was less than 2 Hz. EEG was isoelectric (n = 6) or showed slow polymorphic delta-activity. For therapy, administration of all anaesthetics was terminated, 100% oxygen was delivered and ventilation was increased four-fold. Acidosis was treated by administration of sodium bicarbonate 2-4 mmol litre-1 kg-1. Animals were allocated randomly to one of two groups: group I (control, n = 7) received no dantrolene; group II (n = 8) received dantrolene 2.5 mg kg-1 i.v. All variables were measured over a period of 60 min after therapy: EEG, HR and MAP were recorded continuously and blood-gas tensions, arterial potassium and glucose concentrations and pH were measured every 150 s. In group I (no dantrolene) minor, transient improvements in EEG activity were noted, but all animals died within 15-25 min after the start of therapy. In dantrolene-treated animals, EEG total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement of brain electrical activity during treatment of porcine malignant hyperthermia with dantrolene. 828 May 59

We report on the occurrence of cardiac arrests within a few minutes following succinylcholine in 9 children, all of whom were later shown to have occult neuromuscular disease. Five of the children did not survive the catastrophic event. The anaesthetist in most cases, when discussing premedication, got the impression that the patients were in good health; just in 2 children were there indications of myopathy. Myopathic children coming to surgery and anaesthesia are rare. In these cases the administration of succinylcholine is contraindicated. But the anaesthetist must be aware of the fact that a small number of paediatric patients with unknown/subclinical myopathies might be referred to him. In these cases, without warning muscle rigor, bradycardia and hyperkalemia cardiac arrest may develop within minutes following administration of succinylcholine. The anaesthetist must be prepared for such a challenging event--particularly mentally. Misinterpretation of the symptoms as signs of malignant hyperthermia should be excluded. Resuscitation must start without delay and must continue for more than 30 minutes. Therapeutic attempts to lower extracellular potassium with glucose and insulin must fail for pharmacokinetic reasons. Therapy with intravenous calcium under control of the e.c.g. seems to be the only rational approach to the problem. It is suggested that in every healthy child coming to anaesthesia the physician should consider whether relaxation could not be achieved by other agents. Succinylcholine may well be defined as a "membrane poison"--especially considering the efflux of potassium, myoglobin and creatine kinase from the intracellular space into the bloodstream. The answer to the question asked in the title must therefore be: definitely--yes.
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PMID:[Should the use of succinylcholine in pediatric anesthesia be re-evaluated?]. 836 12

The purpose of this study was to show the behaviour of the plasma level of catecholamines in stress-susceptible pigs during an acute stress and to gain new insights in the role of catecholamines in the initiation of malignant hyperthermia. Therefore, a halothane challenge test was performed in stress-susceptible growing pigs, and the changes of haematocrit, hormones and metabolites were monitored during the handling before the test, during halothane exposure and thereafter. Already in connection with the handling before the test, haematocrit values and plasma levels of epinephrine, norepinephrine, glucose, lactate and potassium increased significantly. However, the plasma concentration of cortisol and free glycerol increased gradually and the level of nonesterified fatty acids did not show any changes. While the levels of catecholamines and potassium decreased already during halothane exposure, haematocrit values and concentrations of glucose and lactate continued to increase. The present results indicate that the catecholamines are not involved in the initiation of malignant hyperthermia.
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PMID:[Effect of acute stress on plasma levels of catecholamines and cortisol in addition to metabolites in stress-susceptible growing swine]. 899 69

Monolayers of the porcine-derived renal epithelial cell line, LLC-PK1, were used to characterize the effects of heat stress on Na+-glucose cotransport. Transepithelial current dependent on 5 mM glucose (I(Glc)), phloridzin-sensitive current (I(phz)), and total transepithelial current (I(total)) were measured as indicators of Na+-glucose cotransport. Severe heat shock (SHS; 45 degrees C for 1 h, then 37 degrees C for measurements) decreased transepithelial electrical resistance (TER), I(Glc), I(phz), and I(total) 50-70%. Mild heat shock (MHS; 42 degrees C for 3 h, then 37 degrees C for 12 h) induced accumulation of 72-kDa heat shock protein (HSP-72), decreased damage to TER from SHS, and prevented damage to I(Glc), I(phz), and I(total). Kinetic analysis showed that SHS damaged and MHS protected total Na+-glucose transport capacity (Vmax of I(Glc)). MHS alone increased TER (50%), I(Glc) (20%), I(total) (20%), and Vmax of I(Glc) (25%). On enhancement of the Na+ gradient by depletion of intracellular Na+, MHS increased I(Glc) 50% and had no effect on transepithelial Na+-dependent sulfate reabsorptive flux measured concurrently or in Na+-replete tissues. These effects of MHS were not reflected in effects on cell survival or luminal membrane surface area as indicated by lactate dehydrogenase or alkaline phosphatase release. In conclusion, HSP-72-inducing heat treatment both protected and enhanced Na+-glucose cotransport independently of the luminal membrane Na+ gradient and selectively with respect to effects on TER, reabsorptive sulfate transport, cell survival, and luminal membrane surface area.
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PMID:Heat shock-induced protection and enhancement of Na+-glucose cotransport by LLC-PK1 monolayers. 936 30

A 6-year-old boy with a rare mitochondrial disease (MELAS: mitochondrial encephalopathy, lactic acidosis, stroke-like episodes) was presented to undergo adenoid resection and bilateral paracentesis. ENT surgery was performed without complications under general anaesthesia using propofol, fentanyl, and ventilation with nitrous oxide and oxygen. Routine intraoperative monitoring (ECG, noninvasive blood pressure, oxymetry and capnometry) was supplemented by frequent body temperature measurements and repeated laboratory analysis of venous blood gases, lactate, and glucose. Clinically, the postoperative course was uneventful and the boy was discharged from hospital on the first postoperative day. Signs or symptoms of malignant hyperthermia never occurred. Laboratory analysis only showed a remarkable serum lactate elevation postoperatively (6 mmol/l) which decreased on the first postoperative day (3.7 mmol/l). The present anaesthesiologic experiences with MELAS-syndrome are limited, and recommendations are mainly based on case reports. Careful preoperative physical examination with special regard to all available medical records, and anaesthetic management comparable with that in malignant hyperthermia susceptible resulted in an uneventful course in our patient. Pathogenetic aspects of mitochondrial diseases focussing on anaesthetic considerations are briefly discussed.
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PMID:[Anesthesia in mitochondrial encephalomyopathies]. 1149 20

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients 'at risk' of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.
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PMID:Hyperglycemic hyperosmolar nonketotic syndrome. 1644 62


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