Objective: The aim of this study was to investigate the cardioprotective effects of lidocaine administered at three different timings, as indexes of hemodynamics, infarct size, antiarrhythmic action, and changing activation time by electrocardiogram in in vivo rabbit hearts. Methods: Thirty two rabbits received regional ischemia by 30 min of left anterior descending coronary artery occlusion followed 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a lidocaine-preconditioned group, a lidocainepostconditioned group, and a lidocaine-continuous administration group. Results: The ratio of areas at risk revealed no significant difference among all groups. Mean infarct size of the area at risk was significantly less in a lidocaine-continuous administration group than other 3 groups. The incidence of arrhythmias during myocardial ischemia was no significant difference between a control group and other 3 groups. The incidence of arrhythmias during reperfusion was no significant difference among all groups. However, lidocaine depressed the activation time which was prolonged by ischemia. Conclusions: It was suggested that lidocaine produced neither preconditioning nor post-conditioning benefits. Lidocaine did not have antiarrhythmic effects during ischemia/reperfusion injury. The clinical implications of this investigation are that lidocaine infusion is no longer recommended for the treatment of ventricular arrhythmias during acute coronary syndrome; however, continuous administration of lidocaine may be effective to make the infarct size small. The prolonged activation time during ischemia was depressed by lidocaine. Thus, it was also indicated that the activation time during ischemia and reperfusion can be normalized by lidocaine. J o u rn al of A n e s th es ia & C li n ic a l Resea rc h