??2-Adrenergic Agonist Effects on Normocapnic and Hypercapnic Cerebral Blood Flow in the Dog Are Anesthetic Dependent

Abstract
α2-Adrenergic receptors are found on large and small cerebral vessels, but their role in control of cerebral blood flow (CBF) and cerebral vascular reactivity is unclear. We assessed the effects of dexmedetomidine (DEX), a highly selective α2-adrenergic agonist, on the cerebrovascular response to hypercapnia in dogs anesthetized with either pentobarbital (PENTO) or isoflurane (ISO), drugs which produce different levels of CBF at a similar level of cerebral oxygen consumption (CMRO2). Dogs were anesthetized with either PENTO, 30 mg/kg, n = 6, or ISO 1.4% end-tidal, n = 7. CBF (radiolabeled microspheres) was determined during normocapnia and hypercapnia at baseline (pre-DEX), after DEX (10μg/kg, intravenous bolus, plus an additional 5μg/kg during hypercapnia), and after administration of a selective α2-adrenergic receptor antagonist (atipamezole, 500μg/kg, intravenous bolus). In the PENTO group, CBF increased from 31 ± 3 to 137 ± 24 mL-min−1 100 g−1 in response to hypercapnia (Pco2 approximately 90 mm Hg) at pre-DEX and there was no change in normocapnic CBF or hypercapnic blood flow after DEX or atipamezole. In the ISO group, at pre-DEX, CBF increased from 86 ± 8 to 166 ± 19 mL min−1 100 g−1 in response to hypercapnia (Pco2 approximately 90 mm Hg). DEX administration was associated with a decrease in both normocapnic (57 ± 4 mL min−1 100 g−1,P<0.05)andhypercapnic(108±ll mL min−1 100 g−1 P < 0.05) CBF without a change in vascular reactivity (pre-DEX, −0.013 ± 0.002 mm Hg mL−1 min−1 100 g−1; post-DEX, −0.016 ± 0.003 mm Hg mL−1 min−1 100 g−1; postatipamezole, −0.012 ± 0.003 mm Hg mL−1 min−1 100 g−1 per mm Hg change in Pco2). In the ISO group, atipamezole restored both normocapnic and hypercapnic flow to pre-DEX level. Pre-DEX CMROz was 2.7 ± 0.4 and 3.1 ± 0.6 mL min−1100 g−1 in the PENTO and ISO groups, respectively, and was not changed by hypercapnia, DEX, or atipamezole. We conclude that although DEX decreases CBF in ISO-anesthetized dogs during both normocapnia and hypercapnia, it does not alter CBF reactivity to hypercapnia.

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