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A Halothane-Induced Biochemical Defect in Muscle of Normal and Malignant Hyperthermia-Susceptible Landrace Pigs

G. Mitchell, BSc, BVSc, PhD^*, J. J. A. Heffron, BSc, PhD, and A. J. J. van Rensburg, MSc

*Senior Lecturer, Department of Physiology, University of the Witwatersrand. Senior Lecturer, Department of Physiological Chemistry, University of the Witwatersrand. Present address: Department of Biochemistry, University of Cork, Cork, Ireland. Senior Professional Officer, Animal and Dairy Science Research Institute, Irene, South Africa.

Abstract

Muscle adenosine triphosphate (ATP), glucose-6-phosphate, phosphocreatine, and pH were measured in nine malignant hyperthermia (MH)-susceptible and 14 MH-resistant Landrace pigs. Muscle biopsies were taken before (under barbiturate anesthesia) and after exposure to halothane. When compared to levels during barbiturate anesthesia, exposure to halothane had no immediate effect on muscle ATP levels in either MH-susceptible or -resistant pigs. However, once malignant hyperthermia developed in susceptible pigs ATP levels decreased significantly. In both susceptible and resistant pigs halothane increased muscle glucoses-phosphate and decreased muscle phosphocreatine and pH significantly below control levels observed during barbiturate anesthesia. In susceptible pigs these changes were significantly more marked than were the changes produced in resistant pigs. These data indicate that the effect of halothane on muscle metabolism is similar in both MH-resistant and -susceptible pigs. The results suggest that the effect of halothane is to inhibit aerobic metabolism by preventing mitochondrial dehydrogenation of pyruvate. Inhibition is complete in susceptible pigs but only retarded in resistant pigs. In susceptible pigs the consequent lactacidosis, hyperthermia, and reduction in ATP synthesis contribute to the development and maintenance of rigidity.

Key Words: HYPERTHERMIA • Malignant • MUSCLE • Skeletal: metabolism • ANESTHETICS • Volatile: halothane.