Dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic brain injury in rats.
OBJECTIVE
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.


METHODS
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 microg.kg(-1).min(-1). At the end of this phase of treatment, the alpha-2 adrenergic antagonist yohimbine was administered (3 mg.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 1microg.kg(-1).min(-1) or 10 microg.kg(-1).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.


RESULTS
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 microg.kg(-1).min(-1) dexmedetomidine, and increased to 119.9% relative to baseline with a dose of 10 microg.kg(-1).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 microg.kg(-1).min(-1) dexmedetomidine and the volume increased to 24.5% in rats treated with 10 microg.kg(-1).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.


CONCLUSIONS
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.
Nakano
Takaaki
T
Department of Anesthesiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara 228-8555, Japan.
Okamoto
Hirotsugu
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology; D014655:Vascular Resistance / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D015016:Yohimbine; D020927:Dexmedetomidine
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