MYOCARDIAL UPTAKE OF BUPIVACAINE .1. PHARMACOKINETICS AND PHARMACODYNAMICS OF LIDOCAINE AND BUPIVACAINE IN THE ISOLATED-PERFUSED RABBIT HEART

Bupivacaine, but not lidocaine, may cause severe cardiac dysrrhythmias in case of accidental intravascular injection. In an attempt to discr iminate between a pharmacokinetic and a pharmacodynamic (or both) orig in to these differences, we used an isolated rabbit heart model with c onstant coronary inflow to compare the myocardial uptake and dispositi on kinetics of lidocaine and bupivacaine. Drug concentration in the ou tflow perfusate was assayed and surface electrocardiogram was recorded . Drug uptake and disposition kinetics were modeled with a two-compart ment open model. An Emax model was used to describe the increase in QR S duration in relation with drug concentration in the central compartm ent. Lidocaine and bupivacaine exhibited similar myocardial pharmacoki netics (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 st eady-state perfusate concentration producing half Emax was the same fo r both drugs. We conclude that bupivacaine-induced QRS widening decrea ses almost at the same rate as does lidocaine-induced QRS widening whe n drug administration is terminated. Therefore, the different cardiac effects of lidocaine and bupivacaine are not due to differences in myo cardial uptake and disposition kinetics.