Bupivacaine suppresses [Ca(2+)](i) oscillations in neonatal rat cardiomyocytes with increased extracellular K+ and is reversed with increased extracellular Mg(2+).

Abstract

Lidocaine is used to treat cardiac arrhythmias, whereas bupivacaine is noted for its cardiotoxicity. A precise mechanism for these differences is unclear, and there is no well defined antidote for local anesthetic cardiotoxicity. Our study compares the effect of lidocaine and bupivacaine on oscillations of intracellular Ca(2+) coupled with contractions in neonatal rat cardiomyocytes by using digital imaging. In medium containing 5.6 mM K(+), both 42 microM lidocaine and 5.5 microM bupivacaine significantly reduced the oscillation rate. The oscillatory patterns were highly irregular, and the rates were increased in the presence of bupivacaine in 7.6 mM K(+) medium, eventually degenerating into a loss of oscillations after several minutes of bupivacaine exposure. Irregular oscillations did not occur with lidocaine until the K(+) concentration was increased to 10 mM. Increasing the Mg(2+) and Ca(2+) concentrations by 2 mM each recovered oscillation that had been suppressed by bupivacaine in high K(+) buffer. Evaluation of intracellular Ca(2+) oscillations in neonatal rat suggests that increased extracellular K(+) may be an important component of bupivacaine cardiotoxicity. Evaluation of intracellular Ca(2+) oscillations in neonatal rat myocytes suggests that increased extracellular K(+) may be an important component of bupivacaine cardiotoxicity.