Dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic brain injury in rats

Dexmedetomidine has been used for purposes of anesthesia and sedation, and experimental studies have demonstrated its neuroprotective effects. However, it has also been shown that the constriction of cerebral vessels in response to high doses of dexmedetomidine decreases cerebral blood flow. We tested the hypothesis that dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic cerebral injury. The effects of dexmedetomidine on cerebral blood flow and mean arterial blood pressure were studied first. Six rats received intravenous infusions of dexmedetomidine in doses ranging from 0.01 to 10 mu g center dot kg(-1)center dot min(-1). At the end of this phase of treatment, the alpha-2 adrenergic antagonist yohimbine was administered (3 mg center dot kg(-1) ip). Cerebral blood flow and mean arterial blood pressure were recorded continuously. A second series of experiments was then performed using a rat model of transient middle cerebral artery occlusion. Forty-two rats received 1 mu g center dot kg(-1)center dot min(-1) or 10 mu g center dot kg(-1)center dot min(-1) dexmedetomidine with or without pretreatment with either of the alpha-2 adrenergic antagonists yohimbine or rauwolscine. Five days after middle cerebral artery occlusion and reperfusion, the rat brains were removed and the infarct volumes were measured. In the first protocol, increasing the dose of dexmedetomidine significantly decreased cerebral blood flow. Mean arterial blood pressure decreased to 79.9% relative to baseline with a dose of 0.01 mu g center dot kg(-1)center dot min(-1) dexmedetomidine, and increased to 119.9% relative to baseline with a dose of 10 mu g center dot kg(-1)center dot min(-1) dexmedetomidine. In the second protocol, the infarct volume in the control group was 9.5% of the total brain volume; the infarct volume increased to 11.3% in rats treated with 1 mu g center dot kg(-1)center dot min(-1) dexmedetomidine and the volume increased to 24.5% in rats treated with 10 mu g center dot kg(-1)center dot min(-1) dexmedetomidine. Pretreatment with an alpha-2 adrenergic antagonist, either yohimbine or rauwolscine, reduced the size of these high-dose dexmedetomidine-induced infarct volumes. Hypertension following the administration of high-dose dexmedetomidine is associated with cerebral hypoperfusion and the exacerbation of ischemic brain injury, possibly through alpha-2-induced cerebral vasoconstriction.