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Anesth Analg 1979; 58:76-81
© 1979 International Anesthesia Research Society
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Skeletal Muscle Mitochondria in Porcine Malignant Hyperthermia

Respiratory Activity, Calcium Functions, and Depression by Halothane

Gerald A. Gronert, MD*, and James J. A. Heffron, PhD{dagger}

*Associate Professor. Department of Anesthesiology, Mayo Medical School, Rochester, Minnesota 55901. {dagger}Senior Research Fellow. Department of Anesthesiology, Mayo Medical School, Rochester, Minnesota 55901.

Abstract

To examine mitochondrial function in malignant hyperthermia, calcium binding and respiratory functions were measured at 37 C in the absence and presence of halothane in mitochondria isolated from the semitendinous muscle of normal and genetically susceptible swine. Oxygen consumption stimulated by a phosphate acceptor, i.e. adenosine diphosphate (ADP), is state 3 respiration; state 4 respiration is that in the absence of ADP. Values for rate of calcium binding and state 3 respiration in susceptible swine were 40 to 60% of those of normal swine. Halothane altered mitochondrial functions in both normal and susceptible swine to a similar degree: with glutamate-malate substrate, halothane markedly inhibited state 3 respiration, had no significant effect on state 4 respiration, and slightly but significantly inhibited the rate of calcium binding. With succinate substrate, halothane slightly inhibited state 3 respiration, slightly stimulated state 4 respiration, and did not alter calcium binding rate. Oxidation of glutamate-malate provides electrons earlier in the cytochrome chain than does oxidation of succinate. The inhibition by halothane of respiration supported by glutamate-malate that was not seen on respiration supported by succinate suggests a mechanism involving the initial energy reactions in electron transfer. Halothane did not release calcium from actively loaded mitochondria. Dinitrophenol uncoupled state 3 respiratory rates similarly, showing that the lower rate in susceptible swine was not due to a limited capacity of the phosphorylating system. The authors conclude that the reduced respiratory and calcium binding activities in mitochondria from susceptible swine support the diagnosis of a myopathy, but that these do not account for the functional and biochemical derangement observed in clinical malignant hyperthermia.

Key Words: HYPERTHERMIA: malignant • METABOLISM: malignant hyperthermia.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1979 by the International Anesthesia Research Society.