Cardiac electrophysiological effects of bupivacaine in the anesthetized dog: relation with plasma concentration

The effects of increasing plasma levels of bupivacaine on sinus node, atrial tissue, atrio-ventricular node, His-Purkinje system and ventricular tissue were evaluated in 16 thiopental-anesthetized dogs. A bolus of bupivacaine administered over 3 min was followed by an infusion over 60 min. Three dosages were administered: 1 mg/kg followed by 0.5 mg/kg/hr in 4 dogs, 2 mg/kg followed by 1 mg/kg/hr in 6 dogs and 4 mg/kg followed by 2 mg/kg/hr in 6 dogs. Electrophysiological parameters of sino-atrial node, atria, atrioventricular node, His-Purkinje system and ventricle and mean aortic pressure were recorded before the administration of bupivacaine (control) and 5, 15, 30, 45 and 60 min after the initial bolus. Blood samples were taken at the same time. On the basis of plasma bupivacaine concentrations, the dogs were divided in 6 groups: group 0 (control), group I (less than 1 microgram/ml), group III (1.5 to 2 micrograms/ml), group IV (2 to 3 micrograms/ml) and group V (greater than 3 micrograms/ml). At plasma concentrations less than 1.5 micrograms/ml bupivacaine prolonged conduction times over the His-Purkinje system and ventricle. At plasma levels greater than 1.5 microgram/ml it depressed also the sinus node and the atrioventricular node functions. No statistically significant difference was found between the control group and the other groups for mean aortic pressure, pH, PaCO2, PaO2 and kalemia. In conclusion, it is suggested that bupivacaine behaves as a class I antiarrhythmic drug at the lower plasma concentrations and as a class I and class IV antiarrhythmic drug at higher plasma concentrations.