To analyze the mechanism of the cerebral vasodilator effect of ketamine in anesthetized rabbits, we measured the internal carotid blood Sow with an electromagnetic flowmeter, the arterial pressure, intracranial pressure, end-tidal CO 2 , and the electroencephalogram. Ketamine injection (1 mg/kg) induced a significant cerebral vasodilatation that was blocked by scopolamine, a cholinergk antagonist. In contrast, the increase in cerebral blood flow after ketamine was additive to the cerebral vasodilator actions of inhaled CO } and of physostigmine infusion, two procedures that activate cholinergic mechanisms. These observations suggest that in rabbits, ketamine activates a cholinergic cerebral vasodilator system. (Stroke 1987;18:445-^49) K ETAMINE is a potent analgesic and dissociative agent used extensively for pediatric anes-, thesia, but which is not recommended for neurodiagnostic or neurosurgical procedures because of its reported tendency to increase intracranial pressure (ICP). "~3 It is generally accepted that the elevation in ICP is secondary to the cerebral vasodilatation that may accompany the alterations in brain electrical activity and possible changes in metabolism elicited by the drug. However, while the cerebral vasodilator effect of ketamine is generally supported, its cerebral metabolic effect is controversial. 13 -3 " 7 If the increase in brain metabolism is inconsistent, it is difficult to understand how this may mediate such a consistent effect as the cerebrovascular dilatation. On the contrary, this apparent poor correlation between cerebral metabolism and blood flow may result from the activation by ketamine of a nonmetabolic mechanism. We studied the cerebrovascular effects of ketamine in rabbits to analyze the possible participation of a neurogenic cholinergic mediator of vasodilatation, using a muscarinic antagonist, scopolamine, and a cholinergic agonist, physostigmine. The existence of such a mechanism has been proposed by others 89 and supported by our work on the vasodilator effect of CO 2 and halothane.
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Materials and MethodsThe experiments were performed on 30 New Zealand white rabbits weighing 2.7-4.1 kg anesthetized inside a box with 5% halothane in air and maintained by mask until a tracheostomy was performed. The animals were then mechanically ventilated with endexpired CO 2 kept at 4%, paralyzed with pancuronium Received May 29, 1985; accepted October 20, 1986. bromide (0.2 mg/kg/hr), and maintained on 0.5-1% halothane in 35% O 2 and N 2 . Respiratory rate was maintained at 40/min and peak inspiratory pressure at 15 cm H 2 O, a combination that maximized the matching between end-tidal CO 2 and PacOj and provided excellent oxygenation, with a Pac^ always above 100 mm Hg. The femoral artery and vein were cannulated for arterial pressure monitoring and drug injection, respectively. Internal carotid blood flow (ICBF) was measured using an electromagnetic flowmeter probe placed around the common carotid artery after the laryngeal, occipital, and external carotid arteries we...
