Objective: To determine the effects of thoracic epidural anesthesia on myocardial infarct size, regional myocardial blood flow (RMBF), and plasma norepinephrine in an anesthetized canine model of ischemia reperfusion injury with infarction. Design: Blinded, randomized, placebo-controlled animal study. Setting: Experiments were performed in the cardiothoracic research laboratory at Wake Forest University Baptist Medical Center. Participants: Anesthetized, open-chest mongrel dogs were used in these studies. Methods: Dogs were instrumented for measurement of aortic pressure (AP) and left ventricular systolic pressure (LVSP), dP/dt, and RMBF. Epidural catheters were inserted at thoracic segment T5. Three groups received epidural 0.5% bupivacaine: low-dose (0 = 7; 0.3 mg/kg bolus, 0.15 mg/kg/h), mid-dose (0 = 7; 0.6 mg/kg bolus, 0.3 mg/kg/h), high-dose (0 = 7; 1.2 mg/kg bolus, 0.6 mg/kg/h). The vehicle (VEH) group received epidural saline. Bolus followed by maintenance infusions began 30 minutes before the onset of ischemia (60 min) and continued through reperfusion (180 min). Results: Myocardial infarct size was significantly reduced in the high-dose group versus the VEH and low-dose groups (p < 0.05). After initiation of the mid and high dose, AP, LVSP, and dP/dt decreased 7% to 16% (high v VEH; p < 0.05). VEH dogs showed a 130% increase from control in early postischemic RMBF. There was a dose-dependent attenuation in this reflow response: 72%, 31%, and 6% increase in RMBF in the low, mid, and high groups, relative to controls (p < 0.05 high v VEH). Although there was no significant difference in plasma norepinephrine, fewer surges occurred in the high-dose group. Conclusions: Thoracic epidural anesthesia reduces infarct size and postischemic hyperemia in a model of ischemia reperfusion injury. Copyright (C) 1999 by W.B. Saunders Company.