Mazoit J X, Orhant E E, Boïco O, Kantelip J P, Samii K
Laboratoire d'Anesthésie-Réanimation, Université Paris-Sud, Le Kremlin-Bicêtre, France.
Anesth Analg. 1993 Sep;77(3):469-76.
Bupivacaine, but not lidocaine, may cause severe cardiac dysrrhythmias in case of accidental intravascular injection. In an attempt to discriminate between a pharmacokinetic and a pharmacodynamic (or both) origin to these differences, we used an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake and disposition kinetics of lidocaine and bupivacaine. Drug concentration in the outflow perfusate was assayed and surface electrocardiogram was recorded. Drug uptake and disposition kinetics were modeled with a two-compartment open model. An Emax model was used to describe the increase in QRS duration in relation with drug concentration in the central compartment. Lidocaine and bupivacaine exhibited similar myocardial pharmacokinetics (i.e., a rapid decrease in the outflow concentration upon drug administration discontinuation). Bupivacaine-induced maximum increase in QRS duration (Emax) was 15 times superior to lidocaine Emax. The steady-state perfusate concentration producing half Emax was the same for both drugs. We conclude that bupivacaine-induced QRS widening decreases almost at the same rate as does lidocaine-induced QRS widening when drug administration is terminated. Therefore, the different cardiac effects of lidocaine and bupivacaine are not due to differences in myocardial uptake and disposition kinetics.
布比卡因而非利多卡因，在意外血管内注射时可能会导致严重的心律失常。为了区分这些差异是源于药代动力学还是药效学（或两者皆有），我们使用了一个冠状动脉血流恒定的离体兔心模型，来比较利多卡因和布比卡因的心肌摄取及处置动力学。测定流出灌注液中的药物浓度并记录体表心电图。药物摄取和处置动力学用二室开放模型进行模拟。采用Emax模型来描述与中央室药物浓度相关的QRS波时限增加情况。利多卡因和布比卡因表现出相似的心肌药代动力学（即停药后流出浓度迅速下降）。布比卡因引起的QRS波时限最大增加量（Emax）比利多卡因的Emax高15倍。产生Emax一半时的稳态灌注液浓度在两种药物中相同。我们得出结论，当停药时，布比卡因引起的QRS波增宽几乎与利多卡因引起的QRS波增宽以相同的速率下降。因此，利多卡因和布比卡因不同的心脏效应并非源于心肌摄取和处置动力学的差异。
