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)

Muscle adenosine triphosphate (ATP), glucose-6-phosphate, phosphocreatine, and pH were measured in nine malignant hyperthermia (MH)-susceptible and 14 MH-resistant Landrace pigs. Muscle biopsies were taken before (under barbiturate anesthesia) and after exposure to halothane. When compared to levels during barbiturate anesthesia, exposure to halothane had no immediate effect on muscle ATP levels in either MH-susceptible or -resistant pigs. However, once malignant hyperthermia developed in susceptibe pigs ATP levels decreased significantly. In both susceptible and resistant pigs halothane increased muscle glucose-6-phosphate and decreased muscle phosphocreatine and pH significantly below control levels observed during barbiturate anesthesia. In susceptible pigs these changes were significantly more marked than were the changes produced in resistant pigs. These data indicate that the effect of halothane on muscle metabolism is similar in both MH-resistant and -susceptible pigs. The results suggest that the effect of halothane is to inhibit aerobic metabolism by preventing mitochondrial dehydrogenation of pyruvate. Inhibition is complete in susceptible pigs but only retarded in resistant pigs. In susceptible pigs the consequent lactacidosis, hyperthermia, and reduction in ATP synthesis contribute to the development and maintenance of rigidity.
 ...
PMID:A halothane-induced biochemical defect in muscle of normal and malignant hyperthermia-susceptible Landrace pigs. 718 63

The effect of dietary magnesium on the post mortem PCr (phosphocreatine) decay in muscle of heterozygote malignant hyperthermia pigs was studied after in vivo exposure to a combination of halothane and succinylcholine. The pigs were anaesthetized with halothane and succinylcholine was injected in the ear vein. Immediately after initiation of the depolarizing neuromuscular blocking effect of succinylcholine the animals were captive-bolt stunned. The PCr decay, reflecting ATP turnover, was followed in situ by 31P-NMR spectroscopy in the biceps femoris muscle for the subsequent 40-70 min post mortem. In 3 of the 4 experiments, the Mg-fed pig had a significantly reduced rate of PCr hydrolysis compared to the control animal. The mechanism of this magnesium effect is unknown.
 ...
PMID:Effect of dietary magnesium on post mortem phosphocreatine utilization in skeletal muscle of swine: a non-invasive study using 31P-NMR spectroscopy. 814 93

Using in vivo 31P-nuclear magnetic resonance spectroscopy, we studied the skeletal muscle metabolism of 17 anesthetized malignant hyperthermia-susceptible piglets and 25 control piglets during and after a halothane stress test. At rest, the phosphocreatine- (PCr) to-ATP ratio was 12% higher in the anesthetized piglets than in the control piglets, which may reflect a higher proportion of fast glycolytic fibers in the former. About 15 min of halothane administration sufficed to provoke onset of a reaction, which was characterized by a reciprocal drop in PCr and an increase in Pi with commencing intracellular acidosis. Halothane was withdrawn after a 20% drop in PCr. Within the next few minutes, intracellular pH dropped sharply and phosphomonoesters (PME) accumulated excessively. ATP was observed to decrease in 8 of the 17 animals. Halothane inhalation provoked a switch of metabolism toward glycolysis. Accumulation of PME suggests a mismatch between glycogenolysis and glycolysis. Despite severe acidification, glycolysis was not completely halted. Recovery of PCr and Pi started approximately 5 min after halothane withdrawal, with a longer time constant for recovery of the former. PME and intracellular pH aberrations lingered and started to recover later. Lost ATP was never restored within the observed recovery period of approximately 20 min.
 ...
PMID:Metabolic response to halothane in piglets susceptible to malignant hyperthermia: an in vivo 31P-NMR study. 822 1

Our aim was to develop an exercise protocol using 31P-magnetic resonance spectroscopy (31P-MRS), which can discriminate between malignant hyperthermia-susceptible (MHS) individuals and controls. MRS spectra of the forearm muscles were recorded at rest, during and after a standardized exercise protocol in 10 MHS patients and compared with spectra obtained in 10 controls. There was no difference in resting intracellular pH (pHi) or PCr/(Pi+PCr) ratio between the groups (PCr = phosphocreatine, Pi = inorganic phosphorus). At the end of the exercise and during the initial recovery phase, the pHi and PCr/(Pi+PCr) ratio were significantly lower in the MHS group ([pHi: 6.37 (0.07) for MHS vs 6.70 (0.05) for controls, P < 0.005; PCr/(Pi+PCr): 0.784 (0.017) for MHS vs 0.954 (0.020) for controls, P < 0.0005]). For PCr/(Pi+PCr), complete separation between the two groups was observed during the initial recovery phase. The mean recovery time of PCr/(Pi+PCr) was 0.57 min for the control group and 1.28 min for the MHS group. The slower recovery of PCr/(Pi+PCr) is likely to be caused by a combination of several factors, including the lower pHi in MHS subjects at the start of recovery (inhibiting ATP production) and excessive sarcoplasmic calcium overload (causing continued enzyme activation and ATP consumption). Our exercise protocol can be a valuable adjunct to discriminate between MHS and non susceptible subjects.
 ...
PMID:Slower recovery of muscle phosphocreatine in malignant hyperthermia-susceptible individuals assessed by 31P-MR spectroscopy. 940 43

31P nuclear magnetic resonance spectroscopy was performed on 19 to 55 kg weighing pigs of different MHS genotypes to study the changes of phosphorus components (inorganic phosphate --Pi, phosphocreatine--PCr and adenosine triphosphate--ATP) of muscle metabolism as well as intramuscular pH under application of halothane. Aim of the present study was to observe the changes in energy metabolism and to perform a comparison with also measured blood parameters. Both, NN and Nn pigs did not show any changes during halothane exposure in phosphorus spectra, but in all animals a partially metabolically compensated respiratoric acidosis was found. In all MHS positive pigs a rapid fall of PCr and a corresponding raise of Pi levels in muscle was observed.
 ...
PMID:[In vivo investigations of stress susceptibility in pigs by means of magnetic resonance spectroscopy]. 941 Jul 28

Twenty four crossbred (Large White, White Meaty, Pietrain, Hampshire) pigs were tested by DNA probe for a mutation on the ryanodine receptor RYR1 (malignant hyperthermia-MH). An equal number of pigs heterozygote (monomutant-MON) and normal on MH (nonmutant-NON) were used in the experiment. The pigs were fed finisher feed (control group) or finisher feed supplemented with magnesium (3.6 g MgO per pig per day; MgO group) for 5 days prior to slaughter. Pigs fed the diet supplemented with MgO had higher plasma Mg concentrations. Phosphorus nuclear magnetic resonance ((31)P NMR) measurements on postmortem (15 min) muscle samples (longissimus muscle) showed the highest phosphocreatine levels in normal pigs fed MgO (P<0.05). The MgO supplementation caused increased Ca(2+) uptake and Ca(2+) ATPase activity only in normal (NON) pigs. ATPase activity was lowest (P<0.05) in heterozygote control pigs. Pigs fed MgO supplemented diet had higher pH (45 min postmortem). A significant lower pH (P<0.05) was obtained in heterozygous (MON) control pigs. Also pigs fed with MgO had lower percentage of drip losses and significant differences (P<0.05) were obtained between heterozygous (MON) pigs. The results indicate that dietary MgO supplementation can improve parameters of muscle energetic metabolism, Ca(2+) uptake and meat quality (pH, drip loss).
 ...
PMID:The effect of dietary magnesium oxide supplementation on postmortem (31)P NMR spectroscopy parameters, rate of Ca(2+) uptake and ATPase activity of M. longissimus dorsi and meat quality of heterozygous and normal on malignant hyperthermia pigs. 2206 35


<< Previous 1 2