Laboratory Investigations

Abstract

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. Objectif : Determiner les effets de l’antagoniste non competitif du recepteur NMDA, la S(+)-ketamine, sur l’evolution neurologique d’un modele rat d’ischemie cerebrale incomplete. Methode : L’isoflurane et un melange d’O 2 (30 %) et de protoxyde d’azote (70 %) ont servi a l’anesthesie, a l’in