Bupivacaine suppresses [Ca2+](i) oscillations in neonatal rat cardiomyocytes with increased extracellular K+ and is reversed with increased extracellular Mg2+

Lidocaine is used to treat cardiac arrhythmias, whereas bupivacaine is note d for its cardiotoxicity. A precise mechanism far these differences is uncl ear, and there is no well defined antidote for local anesthetic cardiotoxic ity. Our study compares the effect of lidocaine and bupivacaine on oscillat ions of intracellular Ca2+ coupled with contractions in neonatal rat cardio myocytes using digital imaging. In medium containing 5.6 mM K+, both 42 mu M lidocaine and 5.5 mu M bupivacaine significantly reduced the oscillation rate. The oscillatory patterns were highly irregular, and the rates were in creased in the presence of bupivacaine in 7.6 mM K+ medium, eventually dege nerating into a loss of oscillations after several minutes of bupivacaine e xposure. Irregular oscillations did not occur with lidocaine until the K+ c oncentration was increased to 10 mM. Increasing the Mg2+ and Ca2+ concentra tions by 2 mM each recovered oscillation that had been suppressed by bupiva caine in high K+ buffer. Evaluation of intracellular Ca2+ oscillations in n eonatal rat suggests that increased extracellular K+ may be an important co mponent of bupivacaine cardiotoxicity.