EFFECTS OF BUPIVACAINE ON CELLULAR OXYGEN-CONSUMPTION AND ADENINE-NUCLEOTIDE METABOLISM

Previous studies on isolated mitochondria have shown an alteration of mitochondrial metabolism by local anesthetics, with an inhibition of adenosine triphosphate synthesis. To show that the same is true for mitochondria intracellularly the effects of the local anesthetic bupivacaine on cellular energy metabolism were studied on cultured fibroblasts. Cells in suspension were analyzed for oxygen consumption using a polarographic method with a Clark electrode, and for cytosol and mitochondrial adenine nucleotides by high performance liquid chromatography. Bupivacaine produced a dose-dependent inhibition of oxygen consumption (50% inhibition at 1.5 mM). After incubation in the presence of bupivacaine, adenosine triphosphate and total adenine nucleotides decreased in the cells, as did the adenylate energy charge. These results demonstrate that bupivacaine interacts with cellular energy metabolism and leads to a depletion of high-energy phosphates. Such intracellular mechanisms could explain in part bupivacaine-induced myocardial depression.