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Eur J Cardiothorac Surg 2000;18:174-181
© 2000 Elsevier Science NL

Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole

^a Department of Cardiovascular Surgery, Hopital Bichat and Xavier Bichat Medical University, Paris, France
^b Institut de Pharmacologie Moléculaire et Cellulaire, CNRS/UPR 411, Valbonne, France
^c Department of Anesthesiology, Hopital Bichat, and Xavier Bichat Medical University, Paris, France

Received 20 September 1999; received in revised form 28 February 2000; accepted 7 March 2000.

Corresponding author. Service de Chirurgie Cardio-vasculaire, Centre Hospitalier Universitaire Xavier Bichat, 46 rue henri Huchard, 75018 Paris, France. Tel.: +33-1-4025-8672; fax: +33-1-4025-6700
e-mail: loic.lang{at}wanadoo.fr

Objective: Recent studies confirmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. Materials and methods: Spinal cord ischemia was induced in normothermia for 14 min in Sprague–Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n=15), control (n=15) receiving only vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. Results: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and definitive paraplegia. Riluzole-treated rats had significantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into 180 multiples of base pairs. Conclusions: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during ‘high risk’ surgical procedures on the thoracoabdominal aorta.

Key Words: Riluzole • Spinal cord ischemia • Excitotoxicity • Aorta

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