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To investigate electrophysiologic and hemodynamic responses to various plasma levels of bupivacaine, especially those in the range normally seen during regional anesthesia, bupivacaine was given intravenously as a bolus dose followed by continuous infusion in pentobarbital-anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. At plasma bupivacaine concentrations below 1000 ng/ml, no significant electrophysiologic or hernodynamic effects mere observed. This indicates that systemic responses to absorbed bupivacaine do not contribute to the cardiac electrophysiologic effects recently demonstrated during thoracic epidural analgesia. At a plasma level of about 2000 ng/ml, a level occasionally achieved during regional anesthesia, bupivacaine prolonged impulse conduction time in all parts of the heart, prolonged atrial and AV nodal refractoriness, decreased left ventricular inotropy, but had no effect on ventricular refractoriness or monophasic action potential duration. These electrophysiologic effects may enhance susceptibility to reentrant arrhythmias.