Effect of local anesthetic ropivacaine on isolated rat liver mitochondria.

Ropivacaine is a new long-acting aminoamide local anesthetic with a reduced systemic and cardiac toxicity. Since the latter seems to be related, at least partially, to an interference with mitochondrial energy transduction, the effect of ropivacaine on the metabolism of rat liver mitochondria was studied. Ropivacaine alone exhibited little effect on mitochondrial metabolism, whereas effects were strongly enhanced by tetraphenylboron (TPB-) anion. At low drug concentrations, state 4 respiration was stimulated and mitochondrial membrane potential collapsed. At higher concentrations, state 4 and uncoupled respiration were inhibited by impairment of electron transfer from NAD- and flavine adenine dinucleotide-linked substrates to the respiratory chain. The fact that TPB- increased drug effects indicated that stimulation of respiration was due to dissipation of the electrochemical proton gradient caused by its electrophoretic uptake, although a classical uncoupling mechanism cannot be excluded. The mechanism for the lower toxicity of ropivacaine in vivo was ascribed to low liposolubility leading to reduced access to the mitochondrial membrane, resulting in a minimal perturbation of mitochondrial metabolism.