Bosnjak Z J, Stowe D F, Kampine J P
Anesth Analg. 1986 Sep;65(9):911-7.
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)
高血药浓度的局部麻醉药具有心脏毒性。本研究旨在比较利多卡因和布比卡因在有氧和无氧及酸中毒情况下，对成年和新生豚鼠体外窦房结细胞固有起搏活动的影响。分离出15对成年（大于80日龄）和新生（0 - 3日龄）豚鼠心脏。将窦房结组织浸浴于37℃的 Krebs - Ringer 溶液中，并分别暴露于浓度递增的利多卡因（0.05 - 0.8 mM）或布比卡因（0.01 - 0.4 mM）中。浸浴液分别用5% CO₂、95% O₂（pH 7.40，PO₂ 482 torr）或12% CO₂、88% N₂（pH 7.01，PO₂ 58 torr）进行平衡。记录窦房结细胞的跨膜动作电位，并将冲动间期换算为频率。我们发现，单纯缺氧和酸中毒会降低成年和新生豚鼠的心率，且这种降低与局部麻醉药的作用具有叠加性。在两个年龄组中，布比卡因降低心率的效力比利多卡因强4 - 5倍。利多卡因抑制新生豚鼠心率的效果约为成年豚鼠的两倍，并且布比卡因导致起搏活动停止的窦房结比例高于利多卡因。我们的研究结果在体外表明，新生豚鼠的窦房结对利多卡因和布比卡因比成年豚鼠的窦房结更敏感，布比卡因在抑制和停止窦房结活动方面效力更强，并且缺氧和酸中毒会增强这些药物引起的起搏抑制作用。（摘要截选至250字）
