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Ann Thorac Surg 1994;58:312-320
© 1994 The Society of Thoracic Surgeons

Articles

Dextrorphan inhibits the release of excitatory amino acids during spinal cord ischemia

Chris K. Rokkas, MD, Loring R. Helfrich, Jr, BS, Douglas C. Lobner, PhD, Dennis W. Choi, MD, PhD, Nicholas T. Kouchoukos, MD*

Division of Cardiothoracic Surgery, Department of Surgery, and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri USA

* Address reprint requests to Dr Kouchoukos Department of Surgery, Jewish Hospital at Washington University Medical Center, 21th S Kingshighway Blvd, St. Louis, MO 63110-1013.


   Abstract
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 Abstract
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The release of excitatory amino acids, particularly glutamate, into the extracellular space plays a causal role in irreversible neuronal damage after central nervous system ischemia. Dextrorphan, a noncompetitive 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 neutotransmitter amino acid concentrations using in vivo microdialysis in a swine model of spinal cord ischemia. After lumbar laminectomies were performed, all animals underwent left thoracotomy and right atrialfemoral cardiopulmonary bypass with additional aortic arch perfusion. Microdialysis probes were then inserted stereotactically into the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid and 15-minute samples were assayed using high-performance liquid chromatography. Group 1 animals (n = 9) underwent aortic clamping distal to the left subclavian and proximal to the renal arteries for 60 minutes. Group 2 animals (n = 7) were treated with dextrorphan before application of aortic clamps, and during aortic occlusion and reperfusion. Five amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and three putative inhibitory neurotransmitters (glycine, {gamma}-amino-butyric acid, and serine). Somatosensory-evoked potentials and motor-evoked potentials were monitored. Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes 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. There was early loss of somatosensory-evoked potentials and motor-evoked potentials during ischemia in group 1 animals. Group 2 animals demonstrated unchanged somatosensory-evoked potentials and only mild (20%) decrease in the amplitude of motor-evoked potentials. These results suggest 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 thoracoabdominal aorta.


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{star} Presented at the Thirtieth Annual Meeting of the Society of Thoracic Surgeons, New Orleans, LA, Jan 31–Feb 2, 1994.

{star}{star} This study was supported in part by grants from the Shoenberg Foundation and Hoffman-LaRoche.


   References
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 Abstract
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