High-dose S(+)- ketamine improves neurological outcome following incomplete cerebral ischemia in rats

Abstract

572CAN J ANESTH 2000 / 47: 6 / pp [572][573][574][575][576][577][578] Purpose: To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. Methods: Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O 2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n=10, control) received fentanyl (bolus: 10 µg·kg -1 iv; infusion 25 µg·kg -1 ·h -1 ) and N 2 O 70% / O 2 . Rats in group 2 (n=10) received O 2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg·kg -1 ·min -1 ). Rats in group 3 (n=10) received O 2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg·kg -1 ·min -1 ). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mmHg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. Results: Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N 2 O -anesthetized controls (9 vs 1 stroke related deaths, P < 0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N 2 O -anesthetized (adrenaline baseline 105.5 ± 92.1 pg·ml -1 , during ischemia 948 ± 602.8 pg·ml -1 , P < 0.05; noradrenaline baseline 407± 120.2 pg·ml -1 , ischemia 1267 ± 422.2 pg·ml -1 , P < 0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71 ± 79.5 pg·ml -1 , ischemia 237 ± 131.9; noradrenaline baseline 317.9 ± 310.5 pg·ml -1 , ischemia 310.5 ± 85.7 pg·ml -1 ). Conclusion: Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge. Résultats : L'évolution neurologique a été meilleure avec de fortes doses de S(+)-kétamine qu'avec l'alfentanyl / N 2 O (9 vs 1 décès reliés à un accident ischémique cérébral, P < 0,05). L'augmentation des concentrations plasmatiques de catécholamines a été plus marquée avec l'alfentanyl / N 2 O (l'adrénaline de base à 105,5 ± 92,1 pg·ml -1 ; pendant l'ischémie, 948 ± 602,8 pg·ml -1 , P < 0,05; la noradrénaline de base à 407± 120,2 pg·ml -1 ; pendant l'ischémie, 1267 ± 422,2 pg·ml -1 , P < 0,05) qu'avec de fortes doses de S(+)-kétamine (l'adrénaline de base à 71 ± 79,5 pg·ml -1 ; pendant l'ischémie, 237 ± 131,9; la noradrénaline de base à 317,9 ± 310,5 pg·ml -1 ; pendant l'ischémie, 310,5 ± 85,7 pg·ml -1 ). Conclusion : L'utilisation de S(+)-kétamine permet une évolution neurologique supérieure après une ischémie cérébrale incomplète. Cette situation peut être reliée à la suppression de décharge sympathique.

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

“…IC, infarct core; scale bar = 250 (m in images a1-d1, a2-d2 and a3-d3. For interpretation of the references to color in this figure legend, the reader is referred to the web version of this paper addition, our results were not in line with experiments that high-dose ketamine improved neurological outcome of cerebral ischemia rats induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 min [41]. This may be explained by the difference of the selected isomers in the present study (ketamine-racemate vs. S (1) ketamine) as well as by the use of different ischemia models.…”

Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion

“…Ketamine, like most anesthetics, has been suggested to have a neuroprotective effect (Reeker et al 2000). The extent to which Ketamine might have protected the brain tissue from ischemia in our study is not known.…”

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

“…19 However, low doses of S(+)-ketamine (0.5 mg·kg -1 ·min -1 ) shifted the autoregulatory curve towards higher MAP values, an effect that is likely related to elevated sympathetic tone of cerebral vessels. 7,19 Increasing the dose of S(+)-ketamine (1.0 mg·kg -1 ·min -1 ) reversed this effect along with a decrease in plasma-catecholamine concentrations. These data suggest that changes in CBF seen in historical studies are unlikely related to impaired CBF autoregulation in humans and animals.…”

“…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. [6][7][8] Although cerebrovascular autoregulation in the rat was intact with S(+)-ketamine, it is unclear whether total iv anesthesia (TIVA) using S(+)-ketamine in combination with propofol affects cerebrovascular autoregulation in humans. Therefore the present study investigates the effects of S(+)-ketamine and propofol (a combination adequate to provide anesthesia during surgery) on the dynamic component of cerebrovascular autoregulation in comparison to sevoflurane anesthesia.…”