title: Comparison of lidocaine and bupivacaine depression of sinoatrial nodal activity during hypoxia and acidosis in adult and neonatal guinea pigs.
abstract: High blood concentrations of local anesthetics are cardiotoxic. The aim of this study was to compare the effects of lidocaine and bupivacaine on the intrinsic pacemaker activity of in vitro sinoatrial nodal cells of the adult and neonatal guinea pig in the presence and absence of hypoxia and acidosis. Fifteen pairs of adult (greater than 80 days old) and neonatal (0-3 days old) hearts were isolated. Nodal tissues were suffused with Krebs-Ringer solution at 37 degrees C and exposed to increasing concentrations of either lidocaine (0.05-0.8 mM) or bupivacaine (0.01-0.4 mM). The suffusate was equilibrated either with 5% CO2, 95% O2 (pH 7.40, PO2 482 torr) or with 12% CO2, 88% N2 (pH 7.01, PO2 58 torr). Transmembrane action potentials were recorded from sinoatrial nodal cells and impulse intervals were converted to rates. We found that hypoxia and acidosis alone reduced rates in both adults and neonates, and that the reduction was additive to the effects of local anesthetics. Bupivacaine was 4-5 times more potent in decreasing rates than was lidocaine in both age groups. Lidocaine was about twice as effective in depressing neonatal rates as adult rates, and bupivacaine caused cessation of pacemaker activity in a greater percentage of nodes than did lidocaine. Our results demonstrate, in vitro, that the neonatal sinoatrial node is more sensitive to lidocaine and bupivacaine than is the adult node, that bupivacaine is more potent in depressing and stopping nodal activity, and that hypoxia and acidosis enhance pacemaker depression caused by these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002045:Bupivacaine / Q000494:pharmacology*; D003864:Depression, Chemical; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D008012:Lidocaine; D002045:Bupivacaine