In vivo effects of dexmedetomidine on laser-Doppler flow and pial arteriolar diameter

Abstract

Background: The α2-adrenergic agonist dexmedetomidine alters global cerebral blood flow (CBF). However, few studies have investigated the action of dexmedetomidine on the cerebral microcirculation. This investigation examined the effects of dexmedetomidine on (1) regional CBF in the rat cerebral cortex using laser-Doppler flowmetry and (2) on pial arteriolar diameter. Methods: Halothane-anesthetized rats were fitted with instruments to measure CBF as determined by laser-Doppler flow (CBF(ldf)) or to measure pial arteriolar diameter by preparing a cranial hollow deepened until a translucent plate of skull remained, thereby maintaining the integrity of the cranial vault. In both groups, 20 μg/kg dexmedetomidine was infused intravenously. Thirty minutes later, the mean arterial pressure was restored to control values with an infusion of phenylephrine (0.5 to 5 μg/kg/min). Results: Administration of dexmedetomidine was associated with decreases in end-tidal and arterial carbon dioxide. The CBF(ldf) and pial arteriolar diameter were measured during normocapnia (controlled carbon dioxide) and during dexmedetomidine-induced hypocapnia. Intravenous administration of dexmedetomidine significantly decreased systemic arterial pressure concurrent with a decrease in CBF(ldf) (22% in normocapnic animals, 36% in hypocapnic animals). Restoration of mean arterial pressure increased CBF(ldf) in normocapnic but not in hypocapnic animals. Similarly, dexmedetomidine significantly reduced pial vessel diameter in both normocapnic (9%) and hypocapnic animals (17%). However, vessel diameters remained decreased in the normocapnic and hypocapnic animals after the mean arterial pressure was restored. Conclusions: These results suggest a modulation of cerebral vascular autoregulation by dexmedetomidine which may be mediated, in part, by alterations in carbon dioxide. Dexmedetomidine may have a direct action on the cerebral vessels to reduce the CBF during normo- or hypocapnia. The differences between CBF(ldf) and peal arteriole responses to restoration of mean arterial pressure may reflect the difference in measurement techniques because laser-Doppler measurements reflect the net effect of several arterial segments on microvascular perfusion, whereas diameter measurements specifically examined individual pial arterioles, suggesting that dexmedetomidine vasoconstriction in the cerebral vasculature may be differentially and regionally mediated.