The differential effect of halothane and 1,2-dichlorohexafluorocyclobutane on in vitro muscle contractures of patients susceptible to malignant hyperthermia

Anesthesia and Analgesia
Christoph H KindlerA Urwyler

Abstract

Malignant hyperthermia (MH) is an autosomal dominant, potentially fatal pharmacogenetic disorder of skeletal muscle. Approximately half of all known MH families show a linkage to the ryanodine receptor type 1 (RY1) gene. Although our knowledge of the diagnosis, genetics, and therapy of MH has improved, the exact pathogenesis and the role of volatile anesthetics as trigger substances for an MH crisis remain unknown. Compounds that do not obey the Meyer-Overton hypothesis (i.e., nonimmobilizers) are today an important part of research on anesthetic mechanisms. We designed this study to test the hypothesis that the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (2N) compared with halothane has different effects on in vitro muscle contractures of muscle bundles from MH-susceptible (MHS) individuals. In vitro muscle contracture tests were performed with either halothane (approximately 660 microM, equivalent to approximately 4 minimum alveolar anesthetic concentration [MAC]) or 2N ( approximately 100 microM, equivalent to approximately 5 times predicted MAC). MAC is defined as the anesthetic concentration that prevents nocifensive movements after a surgical stimulus in 50% of subjects. In contrast to halothane, 2N caused only minim...Continue Reading

References

Jul 15, 1992·Biochemical and Biophysical Research Communications·T J ConnellyR Coronado
Dec 1, 1994·Anesthesia and Analgesia·D D KoblinP Ionescu
Dec 1, 1996·British Journal of Pharmacology·M P MasciaR A Harris
Nov 3, 1998·Lancet·M Denborough
Feb 13, 1999·European Journal of Pharmacology·G R FroemmingK Ohlendieck
Dec 11, 1999·Muscle & Nerve·K Jurkat-RottF Lehmann-Horn
Sep 28, 2001·British Journal of Anaesthesia·A UrwylerUNKNOWN European Malignant Hyperthermia Group

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Citations

Sep 24, 2005·Journal of the American Veterinary Medical Association·Patricia K DranchakJames R Mickelson

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