tacrolimus and Paraplegia

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.. 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.

Topics: Animals; Aorta; Constriction; Male; Neuroprotective Agents; Paraplegia; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Ischemia; Tacrolimus

Intestinal transplants using cadaver donors have become an alternative to total parenteral nutrition (TPN) for the treatment of irreversible intestinal failure. Intestinal transplants using living-related donors have rarely been attempted, and the surgical technique has not been standardized.. We performed a living-related intestinal transplant for a paraplegic, 16-year-old boy with life-threatening TPN complications, including lack of vascular access, recurrent line infections, and intermittent liver dysfunction.. A four antigen-matched donor (father) underwent resection of 200 cm of the ileum on a vascular pedicle comprising the ileocolic artery and vein. This resection left the donor with 300 cm of proximal small bowel, 20 cm of the most distal terminal ileum, the ileocecal valve, and all of the large intestine. The donor's ileocolic artery and vein were anastomosed to the recipient's infrarenal aorta and cava; bowel continuity was restored with an end-to-end anastomosis between the recipient's jejunum and the donor's ileum. Both donor and recipient had uneventful postoperative courses. Recipient maintenance immunosuppression has been with tacrolimus, mycophenolate mofetil, and prednisone. One year after transplant, urine methylmalonic acid indicates good vitamin B12 absorption in both the donor and recipient. The recipient has been completely off TPN since discharge (posttransplant day 21), has gained 20 kg, and has had no evidence of rejection, infection, or graft-versus-host disease.. Intestinal transplants from living-related donors can be lifesaving for selected patients with chronic intestinal failure and can be done with minimal risk to the donor.

Topics: Adolescent; Anastomosis, Surgical; Cholestasis; Histocompatibility Testing; Humans; Immunosuppressive Agents; Intestines; Living Donors; Male; Methylmalonic Acid; Middle Aged; Paraplegia; Parenteral Nutrition, Total; Short Bowel Syndrome; Tacrolimus