Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation.
Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D003975:Diazepam; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D007474:Ion Exchange; D008012:Lidocaine; D008305:Malignant Hyperthermia / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011229:Preanesthetic Medication; D013386:Succinates / Q000378:metabolism; D013552:Swine
D004140:Dinitrophenols; D005971:Glutamates; D013386:Succinates; D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D008012:Lidocaine; D003975:Diazepam; D002118:Calcium; D006221:Halothane