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Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations.
Anesthesiology. 2002 Aug; 97(2):345-50.A

Abstract

BACKGROUND

More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine.

METHODS

Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene.

RESULTS

In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene.

CONCLUSIONS

The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans.

Authors+Show Affiliations

Department of Anesthesiology, University-Hospital Eppendorf, Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12151923

Citation

Fiege, Marko, et al. "Results of Contracture Tests With Halothane, Caffeine, and Ryanodine Depend On Different Malignant Hyperthermia-associated Ryanodine Receptor Gene Mutations." Anesthesiology, vol. 97, no. 2, 2002, pp. 345-50.
Fiege M, Wappler F, Weisshorn R, et al. Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. Anesthesiology. 2002;97(2):345-50.
Fiege, M., Wappler, F., Weisshorn, R., Ulrich Gerbershagen, M., Steinfath, M., & Schulte Am Esch, J. (2002). Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. Anesthesiology, 97(2), 345-50.
Fiege M, et al. Results of Contracture Tests With Halothane, Caffeine, and Ryanodine Depend On Different Malignant Hyperthermia-associated Ryanodine Receptor Gene Mutations. Anesthesiology. 2002;97(2):345-50. PubMed PMID: 12151923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations. AU - Fiege,Marko, AU - Wappler,Frank, AU - Weisshorn,Ralf, AU - Ulrich Gerbershagen,Mark, AU - Steinfath,Markus, AU - Schulte Am Esch,Jochen, PY - 2002/8/2/pubmed PY - 2002/9/11/medline PY - 2002/8/2/entrez SP - 345 EP - 50 JF - Anesthesiology JO - Anesthesiology VL - 97 IS - 2 N2 - BACKGROUND: More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine. METHODS: Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene. RESULTS: In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene. CONCLUSIONS: The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/12151923/Results_of_contracture_tests_with_halothane_caffeine_and_ryanodine_depend_on_different_malignant_hyperthermia_associated_ryanodine_receptor_gene_mutations_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-200208000-00010 DB - PRIME DP - Unbound Medicine ER -