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

Purpose: To determine the effects of the non-competitive NMDA-receptor anta gonist S(+)-ketamine on neurological outcome in a rat model of incomplete c erebral ischemia. Methods: Thirty rats were anesthetized, intubated and mechanically ventilat ed with isoflurane, O-2 30% and nitrous oxide 70%. Following surgery animal s were randomly assigned to one of the following treatment groups: Rats in group 1 (n = 10, control) received fentanyl (bolus: 10 mu g.kg(-1) iv; infu sion 25 mu g.kg(-1).h(-1)) and N2O 70%/O-2. Rats in group 2 (n = 10) receiv ed 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(+)-k etamine (infusion: 1.0 mg.kg(-1).min(-1)). Following 30 min equilibration p eriod ischemia was induced by combined unilateral common carotid artery lig ation and hemorrhagic hypotension to 35 mmHg for 30 min. Plasma catecholami nes were assayed before and at the end of ischemia. Neurological deficit wa s evaluated for three postischemic days. Results: Neurological outcome was improved with high-dose S(+)-ketamine whe n compared to fentanyl/N2O anesthetized controls (9 vs 1 stroke related dea ths, P < 0.05). Increases in plasma catecholamine concentrations were highe r in fentanyl/N2O - anesthetized (adrenaline baseline 105.5 +/- 92.1 pg.ml( -1), during ischemia 948 +/- 602.8 pg.ml(-1), P < 0.05; noradrenaline basel ine 407 +/- 120.2 pg.ml(-1), ischemia 1267 +/- 422.2 pg.ml(-1), P < 0.05) t han in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71 +/- 79.5 pg.ml(-1), ischemia 237 +/- 131.9; noradrenaline baseline 317.9 +/- 31 0.5 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.