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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative study of mechanical and energetic parameters of superfused muscle strips from normal pigs and malignant hyperthermia susceptible (MHS) pigs has been conducted. Phosphorus nuclear magnetic resonance spectroscopy at 80.9 MHz and mechanical measurements were used to assess muscle metabolic state. At rest, biceps femoris biopsies of MHS pigs displayed reduced phosphocreatine level, higher inorganic phosphate, and a more acidic internal pH. In normal stimulated fibers, caffeine infusion (8 or 16 mM) induced twitch potentiation and contracture while twitch tension was reduced and contracture more pronounced in malignant fibers. In normal and malignant fibers, calcium ionophore A23187 produced effects similar to those of caffeine, with the exception of twitch potentiation, which was not observed. With caffeine or A23187, the ATP level remained constant throughout the rest-stimulation-recovery protocol for normal and malignant fibers but phosphocreatine dropped to undetectable levels upon stimulation of malignant fibers. In both treatments some heterogeneity in the resonances of inorganic phosphate was observed in malignant fibers together with a more severe acidosis which might play a role in the impairment of the excitation-contraction process.
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PMID:In vitro correlation between force and energy metabolism in porcine malignant hyperthermic muscle studied by 31P NMR. 165 12

Milan hypertensive (MSH) rats develop hypertension around the 3rd-4th week of life and exhibit increased Na-pump activity in adulthood. The present study was performed to evaluate whether or not hypertension is preceded by an increase in Na-K-ATPase activity. Total and ouabain-sensitive ATPase activities were studied in single microdissected medullary thick ascending limb of Henle (mTAL) tubules from MHS, Milan normotensive (MNS) and Sprague-Dawley (SD) rats at 22-24, 26-28 and 45-60 days of age. Data are given as mean +/- SEM. Total and Na-K-ATPase activity exhibited a developmental pattern in MHS, MNS and SD rats. At 22-24 days no difference was seen between MHS and MNS animals. At 26-28 days MHS had a higher total and Na-K-ATPase activity than MNS (3031 + 171 vs 2471 + 178 pmol phosphate/mm tubule per hour, P less than 0.05; 2289 + 205 vs 1653 + 151, n = 10, P less than 0.05). At this age there was still no difference in mean arterial blood pressure (88 + 4 vs 86 + 3 mm Hg, n = 15). Adult MHS rats had higher blood pressure (140 + 9 vs 112 + 8 mm Hg, P less than 0.001) and higher total (3544 + 136 vs 2718 + 215 pmol phosphate/mm tubule per hour, n = 10, P less than 0.01) and Na-K-ATPase activity (2670 + 99 vs 1942 + 217 pmol phosphate/mm tubule per hour, n = 10, P less than 0.05) than adult MNS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased renal tubular Na-K-ATPase activity in Milan hypertensive rats in the prehypertensive period. 166 81

There are recent reports that inositol phosphate metabolism is involved in the development of malignant hyperthermia (MH). Consequently, we investigated the basal concentration of inositol phosphate products in skeletal and heart muscles of malignant hyperthermia-susceptible (MHS) and healthy control (MHN) swine. Different inositol phosphates were measured by high pressure liquid chromatography, including inositol trisphosphate, tetrakisphosphate, pentakisphosphate and hexakisphosphate. All inositol phosphate products measured had a higher concentration in MHS than MHN in skeletal (304-1330%) as well as heart muscles (134-440%). An activation of the inositol phosphate metabolism has been shown to mobilise intracellular calcium from the sarcoplasmic reticulum. It is therefore concluded that, firstly, besides involvement of the skeletal muscles a primary myocardial abnormality in MHS is possible; and secondly, the idea that the inositol phosphate metabolism could be involved in the development of MH is additionally supported.
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PMID:[Malignant hyperthermia and inositol phosphate metabolism in the heart and skeletal musculature]. 178 4

Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome. Currently, the only accurate means of diagnosing susceptibility to this syndrome is the testing of biopsied skeletal muscle for its contracture response to halothane and caffeine. A less invasive means of diagnosis is needed. The authors previously reported that MH-susceptible patients studied by in vivo phosphorus nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle, as well as a slower postexercise recovery of PCr/Pi, when compared to normal controls. In the present blinded study, the authors compared in vivo 31P NMR determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to in vitro halothane/caffeine contracture test results in 42 patients. Forty-three control subjects were studied to establish normal NMR values of resting Pi/PCr and recovery rate of PCr/Pi. Their findings were compared with those of 27 patients shown to be MH-susceptible and 15 patients MH-negative by contracture testing. The MH-susceptible group had a significantly (P less than 0.005) higher resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/- 0.043) or the control (0.141 +/- 0.026) group. The MH-susceptible group also had a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi-1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group. Twenty-six of the 27 MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and 13 of the 15 MH-negative patients had normal NMR results. Although neither NMR parameter alone was diagnostically reliable, an NMR test utilizing both parameters was quite accurate. The NMR test and contracture test demonstrated an overall agreement of 93% with a copositivity of 96% and conegativity of 87%. The sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8% and 95.3% +/- 20.3%, respectively. The role of 31P NMR in the diagnosis of MH susceptibility and possible mechanisms underlying the observations are discussed.
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PMID:A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic resonance spectroscopy and the in vitro halothane/caffeine contracture test in the evaluation of malignant hyperthermia susceptibility. 185 40

Alpha-adrenoceptor stimulation may induce malignant hyperthermia (MH) in vivo. Consequently, we have investigated the effects of the alpha-adrenoceptor agonist phenylephrine and, for comparison, the effects of the beta-adrenoceptor agonist isoproterenol on inositol-lipid metabolism of malignant hyperthermia susceptible (MHS) and healthy control (MHN) swine. The experiments were performed on electrically stimulated (frequency 0.2 Hz) trabeculae isolated from the right ventricles of the hearts of MHS and MHN animals. After labelling with [3H]inositol for 6 h, different inositol phosphates were measured by high pressure liquid chromatography, including inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate. After stimulation with isoproterenol, the inositol phosphate content did not increase or vary between muscle from MHS and MHN animals. In contrast, all inositol phosphates increased after stimulation with phenylephrine in both muscle types, the effects being greater in MHS than in MHN, especially as regards 1,4,5-IP3 content. As 1,4,5-IP3, a presumed second messenger, has been shown to mobilize intracellular calcium, it is concluded that an enhanced alpha-adrenergic response is involved in the development of MH.
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PMID:Possible involvement of inositol-lipid metabolism in malignant hyperthermia. 206 84

The currently favored theory of pathogenesis of malignant hyperthermia (MH) implicates an abnormality in skeletal muscle calcium ion transport. During a MH crisis a profound lactic acidosis occurs and in MH-sensitive individuals a delayed recovery of venous lactate has been previously noted postexercise. We have used 31P magnetic resonance spectroscopy to follow noninvasively in vivo changes in muscle of intracellular pH and high-energy phosphate metabolites during rest, exercise, and recovery of MH-sensitive subjects. Eleven biopsy-positive MH-sensitive patients have been studied and compared to 26 normal subjects. The MH-sensitive subjects as a group prematurely dropped their intracellular pH during mild aerobic exercise and they demonstrated a marked delay before the recovery of pH after maximal exercise. PCr/(PCr + Pi) ratios also dropped early during exercise but recovered normally. The observed changes in pH and PCr/(PCr + Pi) are consistent with a myopathy in MH-susceptible individuals.
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PMID:Metabolic response to exercise in malignant hyperthermia-sensitive patients measured by 31P magnetic resonance spectroscopy. 237 3

Signs of malignant hyperthermia, including progressive increases in PaCO2, skin temperature and heart rate, and elevated serum levels of potassium, inorganic phosphate, and creatine kinase, were identified in a halothane-anesthetized horse. Treatment was discontinuing halothane administration, applying ice and cold fluids, and hyperventilating with 100% oxygen. After an initial recovery, bilateral hindlimb myopathy and pigmenturia developed. The myopathy resolved after treatment with oral dantrolene, IV fluids, and hydrocortisone. Results of caffeine-halothane challenge, using semimembranosus muscle collected 2 weeks after the episode, were considered within normal limits for horses. The intraoperative abnormalities were evidently predictive of postanesthetic myopathy but the cause in this horse remained unclear.
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PMID:Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. 260 79

Malignant hyperthermia (MH) is a pharmacogenetic disease in man and animals. It primarily involves skeletal muscle tissue, but other tissues might be affected to a lesser degree. Calcium homeostasis in muscle cells is upset in susceptible individuals, so that various agents and circumstances can increase the free, ionised intracellular calcium concentration to damaging levels. The primary defect is not known at present, but is believed to involve an abnormally sensitive calcium-induced calcium release mechanism. Thus small, localised increases in calcium concentration releases more calcium so that a vicious cycle is triggered. The increased calcium concentration causes multiple effects in the muscles by stimulating contraction and a hypermetabolic state, clinically observed as rigidity and fever. If demands on the homeostatic mechanisms to lower the calcium concentration become exhausted, and metabolism is insufficient to supply enough phosphocreatine and ATP, membrane potentials cannot be maintained, and permeability of the cell membranes increase. This causes loss of phosphate and H+ as well as K+ and Mg++, and later myoglobin and creatine kinase. Thereby oxidative metabolism is further impeded with formation of lactate as a result. The ensuing acidosis stimulates sympathetic innervation, resulting in tachycardia, high blood pressure, and vasoconstriction. Hyperkalemia causes arrhythmia. Dantrolene inhibits the release of calcium and can halt the process if given before depletion of the energy rich phosphates is too advanced.
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PMID:Pathophysiology of malignant hyperthermia. 269 55

31Phosphorus-NMR spectroscopy may have the potential to help in the noninvasive diagnosis of malignant hyperpyrexia (MH). Changes in the phosphate-metabolite profile of MH-susceptible (MHS) skeletal muscle occur more readily under conditions of anoxia than in control muscle. Induction of anoxia caused a rapid fall in intracellular phosphocreatine, an elevation of inorganic phosphate, and finally a diminution of ATP in MHS muscle. The onset of metabolic change was slower in control tissue. Increased oxygen consumption may occur in anoxic MHS muscle, which leads to accelerated glycolysis and a rapid fall in the intracellular high-energy phosphates. In MHS muscle an abnormality may exist in carbohydrate metabolism linked with poor resynthesis of the high-energy phosphates, which may be precipitated under anaerobic conditions. Accelerated muscle metabolism is also observed in the presence of 2 mM caffeine and 3% halothane in MHS muscle. Changes in the concentrations of metabolites could be mapped noninvasively under anoxic conditions using topical 31P-NMR.
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PMID:31P-NMR spectroscopy: the metabolic profile of malignant hyperpyrexic porcine skeletal muscle. 272 66

The biochemical characteristics of skeletal muscle mitochondria of malignant hyperthermia (MH) susceptible Dutch Landrace pigs have been investigated before and during an MH attack, induced in vivo by halothane plus succinylcholine. The muscle homogenates have a decreased capacity to synthesize ATP and creatine phosphate during the MH period. Muscle mitochondria prepared from susceptible pigs in an MH period consume less oxygen than do mitochondria isolated before the attack, or mitochondria from control pigs during the challenge. The oxidative phosphorylation is not uncoupled during the critical period. The production of CO2 indicates that the in vitro measured capacity of the MH muscle mitochondria correctly reflects the in vivo condition during the MH attack. The restricted synthesis may be caused by a factor, finding expression in the mitochondria themselves, and obtained or activated during the MH attack.
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PMID:In vivo induced malignant hyperthermia in pigs. II. Metabolism of skeletal muscle mitochondria. 671 Dec 68


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