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 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.
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PMID:Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine. 307 72

The results are reported of the contracture test obtained by using the calcium ionophore A 23187 (Calcimycin) in two patients, the son (A) and the mother (B). The past history of patient A revealed the occurrence of an impending malignant hyperthermia crisis during induction of anaesthesia in 1975. The A 23187 contracture test confirmed the presence of the malignant hyperthermia trait in patient A, whose muscle biopsy had been submitted to the caffeine contracture test, according to Ellis' technique, and found to be positive in the presence of 1 mmol of caffeine in the tissue bath; the contracture test could not be completed with a halothane contracture test, due to the impaired viability of the muscle fibres obtained. On the reverse, the mother (patient B) was found to be negative to the tests applied: the caffeine contracture test, the halothane contracture test and the contracture test performed with the calcium ionophore A 23187. It is suggested the A 23187 contracture test be added to the contracture tests as defined by the European Malignant Hyperpyrexia Group. This test could be of great help in identifying the percentage of relatives of MHS ("malignant hyperthermia susceptible") patients found to be MHE ("malignant hyperthermia equivocal").
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PMID:[Contracture test with ionophore A 23187 for the diagnosis of malignant hyperthermia]. 308 80

Forty patients undergoing diagnostic muscle biopsy as part of investigation for malignant hyperthermia (MH) were given atracurium 0.45 +/- 0.10 mg kg-1 for muscle paralysis. The neuromuscular blockade was antagonized with neostigmine 2.4 +/- 0.4 mg given with glycopyrrolate 0.47 +/- 0.09 mg. Rectal, muscle and skin temperatures and blood lactate concentration and venous Pco2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the regimen of the European MH Group. Fifteen patients were susceptible to MH (MHS), 19 were MH-negative (MHN) and six were MH-equivocal (MHE). No side effects of the drugs were noted. There were no differences between the three groups of patients in any of the measurements.
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PMID:Atracurium and its antagonism by neostigmine (plus glycopyrrolate) in patients susceptible to malignant hyperthermia. 309 48

This paper reviews the associations between RA and three non-MHS genetic markers: C3, Gm, and Pi. There is no evidence to suggest that genes linked to C3 predispose to RA. However, there is evidence to suggest that genes on chromosome 14, linked to both Gm and Pi, do influence susceptibility to RA and further studies of this chromosome are indicated.
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PMID:C3, Gm, and Pi polymorphisms in rheumatoid arthritis. 313 51

Pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males about 6 months old, were exposed to experimental stress. The pigs were either considered normal or shown to be susceptible to develop malignant hyperthermia when tested with halothane at about 6 weeks of age (stress-susceptible pigs). The stress was of the restraint type, produced by two different myorelaxant agents, the depolarizing succinylcholine or the non-depolarizing pancuronium. The blood levels of the catecholamines (CA) noradrenaline (NA) and adrenaline (A) were measured during the stress. The severity of myocardial cell necrosis observed 1 to 2 days after the stress was morphologically graded. In normal pigs the levels of NA during the stress and the degree of myocardial cell necrosis were about the same after both succinylcholine and pancuronium. In stress-susceptible pigs, however, succinylcholine produced very high NA and A levels and severe heart lesions, whereas after pancuronium the NA and A levels were rather low and the heart lesions significantly reduced when compared to those after succinylcholine-induced stress. After pretreatment with dantrolene intravenously the succinylcholine-induced stress only induced slightly increased blood CA levels and no signs of myocardial cell necrosis in pigs susceptible to develop malignant hyperthermia. Dantrolene, an efficient drug in treatment of malignant hyperthermia, probably acts by interfering with release of calcium from the sarcoplasmic reticulum in skeletal muscles. The results indicate that peripheral sympathetic neurones in MHS pigs also react abnormally, probably due to defective calcium turn-over.
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PMID:Disordered catecholamine release in pigs susceptible to malignant hyperthermia. 319 47

A 33 year old woman, with myotonia atrophica and a known susceptibility to malignant hyperthermia, presented during her second pregnancy with multiple episodes of hyperthermia. They were associated with a rapid rise in the serum creatine phosphokinase (CPK) level, and not with infection or a myotonic crisis. Because of the obstetric conditions, caesarean section was planned. Preoperative oral dantrolene was used as prophylaxis. Six days after the start of this treatment, CPK and serum myoglobin levels were back within the normal range. There were no side-effects for the mother nor for the foetus. There were no further increases in either CPK or serum myoglobin levels during surgery or afterwards, but the rectal temperature remained markedly raised for 48 h after the delivery. Oral dantrolene was given during the first nine postoperative days. The occurrence of episodes of high fever during pregnancy linked to MHS and myotonia atrophica is discussed, as well as the anaesthetic management of such a patient. Side-effects of dantrolene for the mother or the foetus are also considered, especially as foetal levels of this drug would seem not to reach therapeutic levels. It would appear interesting to measure maternal dantrolene blood levels, especially if high doses are administered, to avoid reaching therapeutic levels in the foetus.
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PMID:[Oral dantrolene in a parturient with myotonic dystrophy and susceptibility to malignant hyperthermia]. 320 29

The differences observed among rat strains in both basal [Na+]i and the several cation transport systems seem to be due to the different genetic background as clearly shown in F2 populations or after bone marrow transplantation in MHS. The same may be true for humans. In spite of all the caution taken in interpreting the data, because of the great possibility of methodological errors, it is likely that the differences observed in many laboratories are due to uneven genetic or ethnic composition of the samples studied, as shown by Dagher and Canessa. One intriguing observation is that most reports of "low Na-K cotransport" values in hypertensive patients are from Mediterranean countries (Italy, France, and Spain), whereas most reports of "high," or "not low Na-K cotransport," or very high values of countertransport came from populations originating from North Europe (Denmark, USA, South African whites). We are not aware of any study on erythrocyte Na-K cotransport performed in Great Britain (the greatest source of American immigrants). Indeed the difference in cotransport values between North and South European hypertensives might be due to different environmental factors, but if this is so, the difference does not depend on the salt consumption or plasma lipids that are similar in our high and low Na-K cotransport hypertensives (Cusi D et al, submitted). The picture seems relatively less confusing for calcium. The most consistent alterations in different models of hypertension is a decreased Ca-pump in SHR, MHS, and DOCA rats, reduced calcium binding in SHR and MHS, and reduced microsomal ATP dependent calcium uptake in SHR and DOCA rats. [Ca++]i, which is increased in established hypertension in man and rats, is normal in young prehypertensive rats and humans, and returns to normal values after pharmacological treatment of hypertension. This pattern of changes suggests that genetic control of these transport systems is weaker, and probably much influenced by different environmental conditions. However, because of the pivotal role of calcium in vascular smooth muscle cell concentration, its intracellular increase may be the common pathway of the different forms of hypertension. What remains unclear is the relation, if any, between calcium and sodium. Blaustein tried to find a link between them, but his hypotheses have yet to be confirmed.
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PMID:Role of cellular sodium and calcium metabolism in the pathogenesis of essential hypertension. 329 35

Erythrocyte membrane 22Na and 45Ca transport, osmotic stability and antigenic composition were investigated in 3 strains of rats with spontaneous hereditary hypertension (SHR, SHR SP, MHS), as well as normotensive controls for SHR and SHR SP (WKY) and for MHS (MHS). All strains of spontaneously hypertensive rats showed increased passive membrane permeability for sodium, that was due to increased operation rate of the Na+, K+-cotransport system. Metabolizing sodium is increased in the erythrocytes of Japanese rats (SHR and SHR SP), and decreased in Milan rats (MHS), as compared to normotensive controls. After four hours of incubation with orthovanadate, erythrocyte 45Ca levels were 2-3 times as high in SHR and SHR SP as they were in WKY. In the presence of valinomycin, erythrocyte resistance to hypoosmotic hemolysis was essentially higher in SHR and SHR SP than it was in WKY. These differences are related to a changed rate of anion transport through the band 3 protein. There were no differences in this respect between MHS and MNS. An antigen with a molecular weight of 37-39 kD was detected in erythrocyte membranes of WKY and could not be detected in erythrocytes of other rat groups, including the MNS. It is suggested that different molecular origins of membrane disorders may be an immediate cause of different mechanisms of arterial hypertension in Japanese and Milan animals.
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PMID:[Characteristics of the structural-functional status of erythrocyte membranes in 3 strains of rats with spontaneous genetic hypertension]. 335 98

Twenty-seven patients, four of whom had presented with a crisis of malignant hyperthermia and the 23 other being close relatives of such patients, underwent a muscle biopsy so as to determine their susceptibility to malignant hyperthermia. Halothane-caffeine contracture tests, interpreted in accordance with the criteria of the European Group on Malignant Hyperthermia, yielded the following results: 13 positive (MHS), 10 negative (MHN), 4 equivocal (MHE). The history, clinical examination, CPK level, histoenzymatic morphology and electron microscopic study did not provide information sensitive enough to use for the detection of susceptibility to malignant hyperthermia. This confirmed the literature: the halothane-caffeine contracture test remains the only reliable diagnostic test to detect this susceptibility, despite the search for non invasive tests. If the mechanism of triggering a contracture to increasing doses of caffeine is well known in normal muscle, it is the smaller concentrations required which suggests malignant hyperthermia abnormality. The halothane effect is less well understood. A concentration less than or equal to 2 vol % yields a contracture only in MHS muscle. Differences in protocols used by American authors emphasize the importance of standardization as used by the European Group, which is the only way of collecting and comparing results on well over a thousand patients. This confrontation should reduce the number of equivocal diagnoses and allow a correct classification of patients at risk or their relatives as MHS or MHN.
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PMID:[Tests of contracture and sensitivity to malignant hyperthermia in 27 patients]. 336 12

Many similarities in kidney-function abnormalities were found between hypertensive rats of the Milan strain (MHS) and young normotensive human subjects with hypertensive parents, compared with the appropriate controls. These similarities included an increased glomerular filtration rate, increased pressor effect of the kidney after transplantation, increased 24-h urinary output and lower plasma renin activity and urinary kallikrein. The isolated MHS kidney perfused in vitro with an artificial medium had a higher glomerular filtration rate, a higher urinary output, higher tubular sodium reabsorption and higher oxygen consumption than the kidney of control Milan normotensive rats (MNS). Further, reogenic sodium transport across brush border vesicles isolated from proximal tubular cells is faster in MHS than in MNS. Erythrocytes and proximal tubular cells of MHS have a lower volume and sodium content than those of MNS, while sodium transport is faster and the Ca2+-ATPase at Vmax is lower. This indicates that the 'genetic' cellular abnormality responsible for the renal-function abnormality and the hypertension is also present in erythrocytes. Thus these cells may be used to study the genetic cellular mechanisms of hypertension. Experiments with bone marrow transplantation and with F2 hybrids obtained by crossing the F1 (MHS X MNS) hybrids showed that the MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with the hypertension. Since, in human hypertensives, there was a correlation between abnormal erythrocyte sodium transport and renal function, it is proposed that erythrocytes may be used in studying the cellular molecular mechanisms of hypertension.
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PMID:A renal abnormality in the Milan hypertensive strain of rats and in humans predisposed to essential hypertension. 353 35


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