In vitro activity: Bupivacaine solution is cytotoxic to bovine articular chondrocytes and articular cartilage in vitro after only 15 to 30 minutes exposure. Bupivacaine acts in isolated mitochondria, as uncouplers between oxygen consumption and phosphorylation of adenosine diphosphate. Bupivacaine causes a concentration-dependent mitochondrial depolarization and pyridine nucleotide oxidation in isolated mitochondria, which are matched by an increased oxygen consumption at bupivacaine concentrations of 1.5 mm or less at pH 7.4, whereas respiration is inhibited at higher concentrations. Bupivacaine causes the opening of the permeability transition pore (PTP), a cyclosporin A-sensitive inner membrane channel that plays a key role in many forms of cell death. Bupivacaine causes mitochondrial depolarization and pyridine nucleotides oxidation that are matched by increased concentrations of cytosolic free Ca(2+), release of cytochrome c, and eventually, hypercontracture in intact flexor digitorum brevis fibers. Bupivacaine inhibits GIRK channels within seconds of application, regardless of whether channels are activated through the muscarinic receptor or directly via coexpressed G protein G(beta)gamma subunits. Bupivacaine also inhibits alcohol-induced GIRK currents in the absence of functional pertussis toxin-sensitive G proteins. Bupivacaine HCl also potently inhibits cAMP production with an IC50 of 2.3 μM.

Arthroscopy. 2006 Jul;22(7):693-9; Anesthesiology. 2002 Sep;97(3):710-6.