The adenosine triphosphate (ATP) depletion test: Comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility

Britt, Beverley A.; Endrényi, László; Kalow, W.; Peters, P.L.

doi:10.1007/bf03006745

Cited by 41 publications

(3 citation statements)

References 35 publications

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Section: Introductionmentioning

confidence: 99%

“…The primary defect associated with MH susceptibility in man and pigs appears to be located in skeletal muscle (8-10). Abnormal metabolic (8,11,12) and contracture (13,14) responses of skeletal muscle from MH-susceptible man and swine have produced a working hypothesis that abnormal increases in myoplasmic calcium ion concentration stimulate the hypermetabolism and skeletal muscle rigidity observed with the MH syndrome.Additional support for a primary lesion in skeletal muscle of MH-affected man and pigs is the fact that dantrolene, a unique skeletal muscle relaxant is an effective prophylactic and therapeutic agent for MH in man (15) Immedi-ately after biopsy, the muscle was placed on ice and minced with scissors into small pieces and placed in 35-ml centrifuge tubes containing 1.4 ml of 20 mM histidine (pH 6.8) per g of muscle. The muscle was homogenized 15 s X 2, setting of 5, using a Polytron homogenizer with a PT 20 generator (Brinkmann Instruments, Inc., Westbury, NY).…”

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Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Nelson¹

1983

J. Clin. Invest.

137

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A B S T R A C T Two fractions of sarcoplasmic reticulum, one light (LSR) and one heavy (HSR), were isolated from gracilis muscle of control and malignant hyperthermia (MH)-susceptible pigs. Part of the gracilis muscle biopsy was used to compare the contracture sensitivity of the muscle to the calcium-releasing effects of caffeine on isolated SR membranes. Gracilis muscle of MH pigs was more sensitive to the contracture-producing effects of caffeine than control pig muscle. The caffeine dose-cumulative contracture response curve for MH muscle was shifted left of that for controls.The amount of caffeine-induced calcium released from SR is a function of the amount of calcium preload and this did not differ between LSR of MH and control muscle. When LSR fractions were optimally loaded with calcium for caffeine-induced calcium release, no difference in calcium-releasing effects of varying caffeine doses was observed between MH and control LSR. At calcium preloads below optimal, the MH-LSR appeared to be more sensitive to caffeine-induced calcium release. The HSR fractions could not be loaded with calcium in a manner similar to the LSR fractions because of an apparent calcium-induced calcium release phenomenon. Therefore, calcium threshold for calcium-induced calcium release was compared between MH and control HSR fraction. The effect of caffeine on the calcium-induced calcium release was also studied. The average calcium concentration threshold for calcium-induced calcium release was markedly lower for MH vs. control HSR; 20 vs. 63 nmol Ca2+/mg, respectively. Caffeine decreased the threshold for calcium-induced calcium release more in the MH than in control HSR. Under all conditions studied, the amount of calcium released did not differ INTRODUCTIONMalignant hyperthermia (MH)' is a life threatening hypermetabolic syndrome occurring in genetically predisposed man and swine (1-3). In man, MH is usually associated with the administration of certain anesthetic agents (4, 5); whereas in swine the MH syndrome can also be triggered by stress alone (6, 7). The primary defect associated with MH susceptibility in man and pigs appears to be located in skeletal muscle (8-10). Abnormal metabolic (8,11,12) and contracture (13,14) responses of skeletal muscle from MH-susceptible man and swine have produced a working hypothesis that abnormal increases in myoplasmic calcium ion concentration stimulate the hypermetabolism and skeletal muscle rigidity observed with the MH syndrome.Additional support for a primary lesion in skeletal muscle of MH-affected man and pigs is the fact that dantrolene, a unique skeletal muscle relaxant is an effective prophylactic and therapeutic agent for MH in man (15) Immedi-ately after biopsy, the muscle was placed on ice and minced with scissors into small pieces and placed in 35-ml centrifuge tubes containing 1.4 ml of 20 mM histidine (pH 6.8) per g of muscle. The muscle was homogenized 15 s X 2, setting of 5, using a Polytron homogenizer with a PT 20 generator (Brinkmann Instruments, Inc., Westbury, ...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Nelson¹

1983

J. Clin. Invest.

137

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“…A common denominator for malignant hyperthermia susceptibility in humans and pigs is the observed abnormal biochemical (9, 11,14) and pharmacologic (10,ll) responses of skeletal muscle from affected subjects. These abnormal properties of malignant hyperthermia muscle have provided a means to iden-tify malignant hyperthermia susceptibility (4-6, 15,16) and to perform etiologic studies (10,17).…”

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Spectrum of Susceptibility to Malignant Hyperthermia???Diagnostic Dilemma

Nelson

Flewellen

Gloyna

1983

Anesthesia & Analgesia

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Spectrum of susceptibility to malignant hypertherrniadiagnostic dilemma. Anesth Analg 1983;62:545-52. Utilizing established in vitro muscle contracture tests, we have identified three diagnostic contracture phenotypes for malignant hyperthermia susceptibility (MHS) among 103 patients. Phenotype H is an unequivocal diagnostic result for MHS, as is the nonsusceptible phenotype N . The third diagnostic group, phenotype K, represents an equivocal diagnostic response. To provide a basis for understanding relationships between contracture phenotypes and MHS, pigs with phenotypes H , K , and N were exposed to a standardized anesthetic protocol for assessing MHS. During the anesthetic challenge, phenotype H pigs developed a more severe form of the M H syndrome than did phenotype K pigs. Comparing phenotype H v K average responses, Vo, increased four-v twofold; lactate increased 13-v 9-fold; and temperature increased 41.7"C v 39.2"C, respectively. These values either had no change or decreased in the phenotype N pigs. Results of this study suggest that a spectrum of MHS exists among the human population.

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The King syndrome: Malignant hyperthermia, myopathy, and multiple anomalies

McPherson

Taylor

Opitz³

1981

Am. J. Med. Genet.

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Heterogeneity in malignant hyperthermia is being recognized with increasing frequency. In 1973, King described a subgroup of malignant hyperthermia patients with slowly progressive myopathy, short stature, kyphoscoliosis, pectus carinatum, cryptorchidism, and a characteristic facial appearance. Seven cases have been reported, all in males. We present the case of a girl with similar clinical findings who died in a malignant hyperthermia crisis and review the previously reported cases of King syndrome. The delineation of King syndrome provides further evidence for the heterogeneity of malignant hyperthermia and increases awareness of this disorder; its recognition in a female may lead to preoperative diagnosis and prevention of malignant hyperthermia crisis in King syndrome patients.

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The adenosine triphosphate (ATP) depletion test: Comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility

Cited by 41 publications

References 35 publications

Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Spectrum of Susceptibility to Malignant Hyperthermia???Diagnostic Dilemma

The King syndrome: Malignant hyperthermia, myopathy, and multiple anomalies

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