BACKGROUND: Bupivacaine blocks the sodium channels and inhibits the depolarization of myocardium. The inward sodium current (INa) could be activated by decreasing potassium in the extracellualr spaces. We hypothesized that the bupivacaine dose which creates the cardiac toxicity may have the correlation with serum potassium concentration which is in the normal range. METHODS: After the dogs were anesthetized with pentobarbital, 0.5% bupivacaine was administrated at a rate of 0.5 mg/kg/min until SvO2 decreased to 60% or less, which was defined as the point of cardiac depression in this study. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), SvO2, ETCO2, arterial blood gas analysis, serum electrolytes (Na+ , K+ , Ca2+ ), and ECG were taken at baseline and cardiac depression point. Infused bupivacaine dose and blood concentration to make cardiac depression were taken. RESULTS: PaO2, PaCO2, pH, serum electrolytes (Na+ , K+ , Ca2+ ) were within nornal range at baseline and cardiac depression point. MAP, HR, CO, SvO2, and ETCO2 were within normal range at baseline point but decreased significantly at cardiac depression point. Bupivacaine made QRS duration on EKG to prolong significantly. Infused bupivacaine dose to make cardiac depression had an strong negative correlation with concentration of serum potassium (P < 0.05, rs: -. 501). CONCLUSIONS: We conclude that the increase of serum potassium concentration enhances the cardiotoxic effects of bupivacaine, even though it is in the normal range.