NEUROPROTECTION BY THE ALPHA-2-ADRENOCEPTOR AGONIST DEXMEDETOMIDINE IN A FOCAL MODEL OF CEREBRAL-ISCHEMIA

Background. Dexmedetomidine, a highly selective alpha2-adrenoreceptor agonist, decreases central sympathetic activity and reduces the anesth etic requirement of halothane. Preliminary studies show that dexmedeto midine improves the outcome from ischemic injury and, therefore, may h ave potential therapeutic value.Methods: The authors studied 14 rabbit s that underwent a 2-h occlusion of the left internal carotid, anterio r cerebral, and middle cerebral arteries, followed by 4 h of reperfusi on. Ten minutes after occlusion, the animals were treated with either normal saline (n = 7) or dexmedetomidine (n = 7) using a computer-cont rolled infusion rate calculated to maintain a steady state plasma conc entration. Halothane concentration was reduced by 50% for dexmedetomid ine-treated animals to maintain a comparable level of anesthesia. Soma tosensory evoked potentials were used to confirm adequate ischemia, an d injury was assessed by histopathology. Results: There were significa nt differences in the area of ischemic neuronal damage between the gro ups in the cortex (halothane alone, 38.2 +/- 6.0% SEM vs. halothane pl us dexmedetomidine, 20.0 +/- 2.7% SEM, P = 0.018), but not in the stri atum (halothane alone, 68.7 +/- 12.6% SEM vs. halothane plus dexmedeto midine, 43.5 +/- 15.9% SEM, P = 0.24), nor in physiologic parameters. Dexmedetomidine plasma levels obtained every 90 min showed a mean of 4 .0 +/- 0.15 ng/ml. Conclusions: Results from this study indicate that postischemic administration of dexmedetomidine, in a dose that reduces the anesthetic requirements by 50%, has a neuroprotective effect in t his model of focal cerebral ischemia.