DEXTRORPHAN INHIBITS THE RELEASE OF EXCITATORY AMINO-ACIDS DURING SPINAL-CORD ISCHEMIA

The release of excitatory amino acids, particularly glutamate, into th e extracellular space plays a causal role in irreversible neuronal dam age after central nervous system ischemia. Dextrorphan, a noncompetiti ve N-methyl-D-aspartate receptor antagonist, has been shown to provide significant protection against cerebral damage after focal ischemia. We investigated the changes in extracellular neurotransmitter amino ac id concentrations using in vivo microdialysis in a swine model of spin al cord ischemia. After lumbar laminectomies were performed, all anima ls underwent left thoracotomy and right atrial-femoral cardiopulmonary bypass with additional aortic arch perfusion. Microdialysis probes we re then inserted stereotactically into the lumbar spinal cord. The pro bes were perfused with artificial cerebrospinal fluid and 15-minute sa mples were assayed using high-performance liquid chromatography. Group 1 animals (n = 9) underwent aortic clamping distal to the left subcla vian and proximal to the renal arteries for 60 minutes. Group 2 animal s (n = 7) were treated with dextrorphan before application of aortic c lamps, and during aortic occlusion and reperfusion. Five amino adds we re studied, including two excitatory neurotransmitters (glutamate and aspartate) and three putative inhibitory neurotransmitters (glycine, g amma-amino-butyric acid, and serine). Somatosensory-evoked potentials and motor-evoked potentials were monitored. Glutamate exhibited a thre efold increase in extracellular concentration during normothermic isch emia compared with baseline values and remained elevated until 60 minu tes after reperfusion, In animals treated with dextrorphan, glutamate concentrations decreased to one-third of baseline levels before aortic clamping and remained unchanged during ischemia and reperfusion. Ther e was early loss of somatosensory-evoked potentials and motor-evoked p otentials during ischemia in group 1 animals. Group 2 animals demonstr ated unchanged somatosensory-evoked potentials and only mild (20%) dec rease in the amplitude of motor-evoked potentials. These results sugge st that dextrorphan inhibits the release of excitatory amino acids in the spinal cord during ischemia and, therefore, may have a protective effect on spinal cord function during operations on the thoracoabdomin al aorta.