BACKGROUND: The use of ketamine as the sole anesthetic induces marked central sympathetic stimulation, causing an increase of heart rate and blood pressure. alpha2-receptor agonist has been demonstrated to attenuate many of these undesirable effects when used as a premedicant. Brimonidine is a new and highly selective alpha2-receptor agonist, and rauwolscine is a selective alpha2-receptor antagonist with little affinity for imidazoline receptors. Using power spectral analysis of heart rate variability, this study examines the effect of brimonidine premedication during ketamine anesthesia on the changes in the autonomic nervous system. METHODS: From 57 Sprague-Dawley rats, 12 rats were anesthetized by urethane (U Group, 1.5 g/kg), 18 rats by ketamine (K Group, 100 mg/kg, 2 mg/kg/min continuous infusion) intraperitoneal injection after saline premedication. Brimonidine (BK Group, 30 microgram/kg, n=15), brimonidine with rauwolscine (BRK Group, 30 microgram/kg, 20 mg/kg, n=12) were adminstered as a premedicant before induction of ketamine anesthesia. ECG signals were recorded for 5 min after a period of 10 min of anesthetic stabilization. Power spectal analysis of the data was computed, using short-time Fourier transform. The spectral peaks within each measurement were calculated; a low frequency area (0.04~1.0 Hz), a high frequency area (1.0~5.0 Hz), and a total frequency area (0.04~5.0 Hz) were measured. RESULTS: The results documented that the K Group showed sympathetic activation as compared with the U Group (p<0.001). The BK Group showed sympathetic depression compared with the K and BRK Groups (p<0.001). There were no significant differences in sympatho-vagal balance between the K and BRK Groups. CONCLUSIONS: These results suggest that premedication with brimonidine is effective in attenuating the sympathetic stimulatory effect of ketamine.