Cholinergic cerebral vasodilator effect of ketamine in rabbits.

Abstract

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. 10 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...

Craniosacral Therapy: The Effects of Cranial Manipulation on Intracranial Pressure and Cranial Bone Movement

“…Ketamine has been shown to increase ICP by causing cerebral vasodilatation. 39 Coronal suture movement, as measured from the radiographs taken prior to and during the applied distractive forces, did not occur at forces between 5 to 20 g. No significant difference was found between the average amount of movement (distraction measurement minus baseline measurement) at any of the applied forces between 5 to 20 g. To determine if ICP change or coronal suture movement would occur at higher loads of frontal bone distraction, the last animal (2833) underwent additional distractive forces of 100, 500, 1000, 2000, 5000, and 10 000 g applied to the frontal bone. ICP remained constant until 1000 g of distraction, following which it decreased from 3 to 2 mm Hg.…”

“…Research has shown that Ketamine increases ICP by causing cerebral vasodilatation, 39 but that the effects of Ketamine on ICP are short-lived and that reliable results can be obtained. 5 The dosages of Ketamine in this experiment were consistently maintained based on the animal's mass, and each procedure was consistently timed; so even if this anesthetic caused an increase in ICP, all of the animals would have been affected in the same manner.…”

Effects of Dextromethorphan on Regional Cerebral Blood Flow in Focal Cerebral Ischemia

“…In isolated feline middle cerebral arter ies, thienylcyclohexylpiperidine (TCP) had no ef fects on vascular tone (Duverger et al, 1987). On the other hand, ketamine was found to increase ce rebral blood volume in dogs (Artru and Katz, 1989), and increase global CBF in rabbits (Reicher et al, 1987). In Wi star rats subjected to middle cerebral artery occlusion, MK-801 was found to increase rCBF in the ischemic territory (Buchan et al, 1989).…”

Effect of ketamine on cerebral cortical blood flow and metabolism in rabbits.

“…Two to four minutes after the injection of ketamine, H 2 inflow was stopped and arterial and venous samples were again taken. This approach, based on our observations with volumetric flow measurement and the findings of Reicher et al, 9 allowed estimation of the highest blood flow, which peaks at 2-4 minutes and remains at this level for another 7-8 minutes. Such stability of flow is necessary for quantitative validity of both H 2 clearance and O 2 consumption measurements.…”

“…We were interested in evaluating the possible cerebral metabolic effect of ketamine in a rabbit preparation to elucidate the role of a cholinergic cerebral vasodilator mechanism activated by ketamine recently proposed by Reicher et al 9 to explain their findings.…”