KETAMINE DECREASES PLASMA-CATECHOLAMINES AND IMPROVES OUTCOME FROM INCOMPLETE CEREBRAL-ISCHEMIA IN RATS

Central neuroexcitatory receptors (N-methyl-D-aspartate [NMDA], non-NMDA) may affect outcome from cerebral ischemia by altering sympathetic nervous system activity. We tested whether ketamine, an NMDA antagonist, and NBQX, a non-NMDA antagonist, improve outcome from incomplete cerebral ischemia in the rat and whether a change in outcome is related to changes in plasma catecholamines. There were five treatment groups: group 1 (control, n = 10) received a fentanyl infusion at a rate of 25-mu-g.kg-1.h-1 and ventilation with 70% N2O in O2. Group 2 (n = 10) received the same anesthetic treatment and were given an intraperitoneal injection of 30 mg/kg NBQX 15 min prior to ischemia. Group 3 (n = 10) received a ketamine infusion of 1.0 mg.kg-1.min-1 and ventilation with room air. Group 4 (n = 10) received a ketamine infusion of 1.5 mg.kg-1.min-1. Group 5 received a ketamine infusion of 1 mg.kg-1.min-1 plus a 6 ml/kg intraperitoneal injection of 40% glucose solution 15 min before the start of ischemia. Ischemia was produced by right common carotid ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Blood gases, pH, and skull temperature were controlled during ischemia. Plasma glucose increased during ischemia in all groups but was lower in ketamine-anesthetized rats (groups 3 and 4). Glucose-loaded ketamine-anesthetized rats (group 5) had plasma glucose concentrations similar to the control group. Plasma epinephrine and norepinephrine concentrations were significantly less in ketamine-anesthetized rats (groups 3, 4, and 5) during ischemia compared to controls (P < 0.05). Neurologic outcome was significantly better (P < 0.05) in all ketamine-treated rats (groups 3, 4, and 5) compared to the control group, regardless of plasma glucose concentration during ischemia. NBQX did not improve neurologic outcome. These results suggest that ketamine improves neurologic outcome from incomplete cerebral ischemia by a mechanism related to a decrease in plasma catecholamine activity.