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Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo
N G Burdett1, D K Menon, T A Carpenter
1Herchel Smith Laboratory for Medicinal Chemistry, Cambridge, UK.
Abstract:
Autoradiographic studies have shown that low dose ketamine produces increases in regional glucose utilisation and blood flow in the hippocampus, cerebral cortex, and olfactory lobe in the rat brain, probably due to antagonism at the NMDA receptor. Functional MRI using deoxyhaemoglobin contrast can be used to study changes in regional cerebral blood flow (rCBF). Long TE gradient-echo sequences were used to study changes in rCBF produced by low dose ketamine in rats anaesthetised with nitrous oxide, supplemented with either halothane (HAL) or fentanyl/fluanisone/midazolam (FFM) combination. Images from rats in the FFM group showed a 10-14% increase in signal intensity in the hippocampus, cerebral cortex, and olfactory lobe following either a single bolus or a low dose infusion of ketamine (p < .05). These changes were significantly reduced in the HAL group (p < .005). Halothane is known to attenuate the changes in regional glucose utilisation produced by the noncompetitive NMDA antagonist dizocilpine (MK-801), and its effects on ketamine-induced changes in rCBF seen in this study may be due to a similar effect. The potential use of functional MRI in studying the effect of pharmacological interventions on rCBF is discussed.
Insights
Low dose ketamine increases brain blood flow in rats, particularly in the hippocampus and cortex. Anesthetic choice significantly impacts these ketamine-induced changes in regional cerebral blood flow (rCBF).
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Autoradiography shows ketamine increases glucose utilization and blood flow in rat brain regions (hippocampus, cortex, olfactory lobe).
- This effect is likely due to antagonism of the N-methyl-D-aspartate (NMDA) receptor.
- Functional magnetic resonance imaging (fMRI) with deoxyhemoglobin contrast can measure regional cerebral blood flow (rCBF) changes.
Purpose of the Study:
- To investigate the effects of low-dose ketamine on rCBF in rats using fMRI.
- To compare the influence of different anesthetic regimens (halothane vs. fentanyl/fluanisone/midazolam) on ketamine-induced rCBF changes.
Main Methods:
- Rats were anesthetized with nitrous oxide, supplemented with either halothane (HAL) or a fentanyl/fluanisone/midazolam (FFM) combination.
- Long TE gradient-echo sequences were used to acquire fMRI images.
- Changes in signal intensity, reflecting rCBF, were measured after ketamine administration (bolus or infusion).
Main Results:
- Ketamine administration led to a significant 10-14% increase in signal intensity (rCBF) in the hippocampus, cerebral cortex, and olfactory lobe in rats anesthetized with FFM (p < .05).
- These ketamine-induced rCBF increases were significantly attenuated in rats anesthetized with halothane (p < .005).
Conclusions:
- Functional MRI can effectively study pharmacological effects on rCBF.
- Halothane anesthesia may attenuate ketamine's effects on rCBF, potentially via a mechanism similar to its effect on NMDA receptor antagonists like dizocilpine (MK-801).
- Anesthetic choice is a critical factor when evaluating ketamine's impact on brain hemodynamics using fMRI.