Effect of pH and halothane on muscle and liver mitochondria.

MITCHELSON, K. R., AND F. J. R. HIRD. Effect of pH and halothane on muscle and liver mitochondria. Am. J. Physiol. 225(6) : 1393-l 398. 1973.-The separate and combined effects of hydrogen ions and of the anesthetic halothane on skeletal muscle mitochondria have been studied using pyruvate plus malate as the substrate. Below pH ‘6.5 and pH 6.0 there was a rapid fall in State 3 respiration and the ADP/O ratio, respectively. The State 3 respiration was very sensitive to halothane, and the ADP/O ratio became increasingly sensitive above 3 mu halothane. Hydrogen ions and halothane which, when present singly, at low concentrations have small effects on mitochondrial function, have marked effects when present together. The results indicate little inhibition of mitochondrial respiration at hydrogen ion concentrations found by other workers following exercise to exhaustion. The genetic disease, malignant hyperpyrexia, is characterized by a high intramuscular hydrogen ion concentration during anesthesia (often halothane). Pronounced inhibition of mitochondrial respiration occurred under similar conditions. The results are discussed in relation to muscle contraction and to malignant hyperpyrexia.