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NEUROSURGICAL ANESTHESIA

The Effects of FK506 on Neurologic and Histopathologic Outcome After Transient Spinal Cord Ischemia Induced by Aortic Cross-Clamping in Rats

Loïc Lang-Lazdunski, MD, PhD^*, Catherine Heurteaux, PhD, Hervé Dupont, MD, Danielle Rouelle, BA, Catherine Widmann, BA, and Jean Mantz, MD, PhD

*Department of Cardiovascular Surgery, Bichat University Hospital and Xavier Bichat Medical University, Paris, France; Institute of Molecular and Cellular Pharmacology, Valbonne, France; and Department of Anesthesiology, Bichat University Hospital and Xavier Bichat Medical University, Paris, France

Address correspondence and reprint requests to Dr. Loïc Lang-Lazdunski, Service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France. Address e-mail to loic.lang{at}wanadoo.fr

Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery. We investigated the effect of the immunosuppressant FK506, a macrolide antibiotic demonstrated to have neuroprotective effects in cerebral ischemia models, in a rat model of transient spinal cord ischemia. Spinal cord ischemia was induced in anesthetized rats by using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at the onset of reperfusion. Neurologic status was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia). Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology. Physiologic variables did not differ significantly among experimental groups. All control rats suffered severe and definitive paraplegia. FK506-treated rats had significantly better neurologic outcome compared with control. Histopathologic analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury. These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping.

Implications: A single dose-injection of the immunosuppressant FK506 significantly improved neurologic outcome and attenuated spinal cord injury induced by transient thoracic aortic cross-clamping in the rat.

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