Ketamine Effects on Local Cerebral Blood Flow and Metabolism in the Rat

Abstract

The effects of an anesthetic dose (100 mg/kg) of ketamine, a phencyclidine derivative, on local rates of cerebral glucose utilization (LCGU) and CBF (LCBF) have been investigated by the quantitative [14C]2-deoxy-glucose and [14C]iodoantipyrine techniques in the unparalyzed, spontaneously breathing rat. In ketamine-injected animals, LCGU was significantly increased in some limbic structures and decreased in inferior colliculus, vestibular, and cerebellar nuclei. The degree and spatial distribution of drug-induced changes was similar for local blood flow rates, LCBF being increased in limbic regions and decreased in the inferior colliculus. Although Paco2 values were higher in anesthetized animals, the pattern of LCBF/LCGU ratios was not significantly affected by ketamine in the 36 brain regions examined in this study. So, at least in the rat and at the anesthetic level studied here, a net vasodilatory in vivo effect was not observed. These results support the hypothesis that CBF changes induced by the drug in animals and man are primarily related to the metabolic effects exerted by ketamine on cerebral structures.

Differential Effects of Antipsychotic and Glutamatergic Agents on the phMRI Response to Phencyclidine

“…Several lines of evidence support the suggestion that the observed pattern of activation is representative of the central effects of PCP in freely moving animals and in humans. First, the observation of activation in response to PCP is consistent with the excitatory effects of NMDAR antagonists observed in freely moving rodents, measured with single unit recording (Homayoun et al, 2005), [ 14 C]-iodoantipyrine CBF measurements (Cavazzuti et al, 1987), and 2DG Duncan et al, 1998aDuncan et al, , b, 1999bDuncan et al, , 2000Weissman et al, 1987;Meibach et al, 1979). Second, the anatomical distribution of rCBV changes is consistent with regions of increased 2DG uptake in conscious rats upon injection of NMDAr antagonist such as PCP, ketamine, or MK-801 (Duncan et al, 1999a).…”

S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans

“…However, recent investigations showed that ketamine or its enantiomere S(+)-ketamine meets most of the above mentioned criteria: ketamine as a single anesthetic or in combination with benzodiazepines, propofol or isoflurane does not affect ICP 1-3 or the coupling between CBF and CMR. 4 Likewise, recovery of postoperative psychomotor function and performance was more rapid with the enantiomere S(+)-ketamine compared to racemic ketamine. 5 In animal models of cerebral ischemia and traumatic head injury ketamine and its enantiomere S(+)-ketamine showed brain protective potential even when administered one hour after the insult.…”

Lack of effect of L‐687,414 ((+)‐cis‐4‐methyl‐HA‐966)5 an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology

“…Heightened blood flow may remove lactate accumulated as a result of the maintenance of intracellular ionic homeostasis by glycolysis during the intense activation of cingulate neurones. Interestingly, following ketamine administration, cerebral blood flow was also found to increase in excess of metabolic demand within the cingulate cortex (Cavazzuti et al, 1987).…”